[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-head-and-neck-squamous-cell-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-head-and-neck-squamous-cell-carcinoma":35},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,19,0,[8,64,185,216,247,273,313,340,379,405,427,461,499,528,560,581,601,625,645],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":52,"lastUpdatePostDateStruct":53,"startDateStruct":56,"completionDateStruct":58,"leadSponsor":60,"locationsCount":63},"100449723","phase-2-bicazo-a-study-combining-two-immunotherapies-cabozantinib-and-nivolumab-to-treat-patients-with-advanced-melanoma-or-squamous-cell-head-and-neck-cancer-an-immunomatch-pilot-study-100449723",false,"NCT05136196","BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study","Biomarker Stratified CaboZantinib (NSC#761968) and NivOlumab (NSC#748726) (BiCaZO) - A Phase II Study of Combining Cabozantinib and Nivolumab in Participants With Advanced Solid Tumors (IO Refractory Melanoma or HNSCC) Stratified by Tumor Biomarkers - an immunoMATCH Pilot Study","Inclusion Criteria:\n\n* STEP 1 - SPECIMEN SUBMISSION\n* Participants must have histologically confirmed melanoma that is stage III or IV, unresectable, recurrent, or metastatic non-uveal melanoma OR Participants must have histologically confirmed squamous cell carcinoma of the head and neck (HNSCC) that is either locally recurrent and non-amendable to curative therapy (e.g., radiation, surgery) or metastatic. The primary tumor location must be the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor site of nasopharynx (any histology) or unknown primary tumor are not eligible\n\n  * Note: For participants with primary oropharyngeal cancer, human papillomavirus (HPV) or p16 status must be known prior to step 1 registration\n* Participants must have disease presentation consistent with measurable disease. Note: Current disease measurements will not be required until step 2 registration\n* Participants must have had documented progression during or within 12 weeks after the last dose of PD-1 checkpoint inhibition-based therapy. Participants must have been receiving checkpoint inhibition for a minimum of 6 weeks. Participants who recur during adjuvant anti-PD1 treatment or within 12 weeks of completion of adjuvant anti-PD1 treatment are eligible if they have measurable disease and are considered unresectable\n* Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test within 6 months prior to step 1 registration\n* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days prior to step 1 registration\n* Participants with a history of hepatitis C virus (HCV) infection must have no detectable viral load within 28 days prior to step 1 registration\n* Participants must not have an active infection requiring systemic therapy (except HBV, HCV or HIV as mentioned above)\n* Participants must not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 90 days prior to step 1 registration, unless clinically stable with ongoing medical management\n* Participants must have recovered to baseline or =\\\u003C grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 toxicities related to any prior treatments, unless adverse events are deemed clinically nonsignificant by the treating investigator or stable on supportive therapy\n* Participants must not have received more than one prior primary radiotherapy regimen, curative or adjuvant, to the mucosal surfaces of the head and neck, with the additional following criteria:\n\n  * If the primary radiation is combined with chemotherapy, a minimum of 16 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration. If the radiation is given alone, a minimum of 8 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration\n  * Additional palliative radiotherapy regimens are permitted but cannot have been administered to previously treated tissue (i.e., overlapping fields are excluded) with the exception of central nervous system (CNS) radiation and must be completed at least 4 weeks prior to step 1 registration\n  * Treatment areas should be healed with no sequelae from radiation therapy (RT) that would predispose to fistula formation\n* Participants must not have received prior treatment with anti-VEGF therapies for any reason\n* Participants must be \\>= 18 years of age\n* Participants must have a Zubrod Performance Status 0 or 1\n* Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and must be class 2B or better to be eligible for this trial\n* Participants must not have any known significant organ disfunction that, in the opinion of the treating investigator, may impact suitability for receiving combination nivolumab\u002Fcabozantinib treatment\n* Participants must be able to take oral medication without breaking, opening, crushing, dissolving or chewing capsules\n* Participants must not have malabsorption syndrome\n* Participants must not have active autoimmune disease requiring systemic steroids (equivalent of \\> 10mg of prednisone) or other immune suppression. Exceptions:\n\n  * Type 1 diabetes mellitus\n  * Endocrinopathy only requiring hormone replacement\n  * Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment\n  * Conditions not expected to recur in the absence of an external trigger\n* Participants must not have received an organ allograft\n* Participants must not have a history of hemoptysis (defined as \\>= 1\u002F2 tsp of bright red blood per day) or tumor bleeding within 90 days prior to step 1 registration\n* Participants must not have any of the following criteria due to the possibility of increased risk for tumor bleeding with cabozantinib therapy:\n\n  * Prior carotid bleeding\n  * Tumors that invade major vessels (e.g., the carotid) as shown unequivocally by imaging studies\n  * Central (e.g., within 2 cm from the hilum) lung metastases that are cavitary as shown unequivocally by imaging studies\n  * Any prior history of bleeding related to the current head and neck cancer\n  * History of gross hemoptysis (bright red blood of 1\u002F2 teaspoon or more per episode of coughing) within 3 months\n* Participants must not require concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel)\n\n  * Participants must not require anticoagulants except for the following:\n\n    * Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).\n    * Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors, rivaroxaban, edoxaban, or apixaban in participants without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to step 1 registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor\n* Participants must not have evidence of preexisting uncontrolled hypertension 28 days prior to step 1 registration as documented by baseline blood pressure reading with systolic blood pressure \\> 150 mmHg and\u002For diastolic blood pressure \\> 90 mmHg. Participants on antihypertensive therapies with controlled blood pressure are eligible\n* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen\n* Participants must not be pregnant or nursing due to the known safety profiles of the drugs in this study. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of \"reproductive potential\". In addition to routine contraceptive methods, \"effective contraception\" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation\u002Focclusion and vasectomy with testing showing no sperm in the semen\n* Have an adequate archival tissue specimen verified by the local pathologist and documented on the Pathology Review Form from a procedure obtained after the development of resistance to anti-PD-1\u002FL1 therapy. Archival tissue must consist of tumor block or at least 1 hematoxylin and eosin (H\\&E)-stained 4-5 micron slide and 20 freshly cut serially sectioned and numbered 4-5 micron unstained, uncharged slides OR\n\nBe willing to undergo research biopsy AND have tumor accessible for biopsy based on the following criteria:\n\n* Mediastinal, laparoscopic, gastrointestinal, or bronchial endoscopic biopsies can be obtained incidentally to a clinically necessary procedure and NOT for the sole purpose of the clinical trial\n* Acceptable biopsy procedures are:\n\n  * Percutaneous biopsy with local anesthetic and\u002For sedation with an expected risk of severe complications \\\u003C 2%\n  * Direct transoral biopsy (with or without local anesthetic and\u002For sedation) with an expected risk of severe complications \\\u003C 2%\n  * Excisional cutaneous biopsy with local anesthetic and\u002For sedation with an expected risk of severe complications \\\u003C 2%\n  * Biopsy with removal of additional tumor tissue during a medically necessary mediastinoscopy, laparoscopy, gastrointestinal endoscopy, bronchoscopy or craniotomy. No open surgical, laparoscopic or endoscopic procedure should be performed solely to obtain a biopsy for this protocol\n  * Removal of additional tumor tissue during a medically necessary surgical procedure\n\n    * Participants must submit whole blood for germline genomic analysis\n    * Participants must have been offered the opportunity to participate in specimen banking\n    * Note: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system\n* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines\n* Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)\n\n  * STEP 2 TREATMENT REGISTRATION\n* Note: No tests or exams are required to be repeated for step 2 registration (Treatment). However, participants who are known to have a change in eligibility status after step 1 registration are not eligible for step 2 registration\n\n  * Participants must continue to meet eligibility for step 1 registration prior to step 2 registration\n  * Participants must have had their tumor tissue submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System prior to step 2 registration\n  * Participants registered during stage II of the protocol must have received assignment to an open cohort from the SWOG Statistics and Data Management Center based on their biomarker screening profile (not applicable for patients registered during stage I of the protocol)\n  * Participants must have measurable disease. All measurable disease must be assessed within 28 days prior to step 2 registration. All non-measurable disease must be assessed within 42 days prior to step 2 registration. Note: All disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors \\[RECIST\\] 1.1)\n  * For melanoma participants, CT chest, abdomen and pelvis must be obtained. For HNSCC participants, CT neck and chest must be obtained. Further imaging (i.e., MR brain, CT abdomen\u002Fpelvis or extremities, bone scan) will be performed as deemed appropriate by the treating physician\n  * Participants with treated brain metastases must have no evidence of progression on the follow-up brain imaging after central nervous system (CNS)-directed therapy\n  * Participants must not have experienced any significant health changes that, in the opinion of the treating investigator, may impact continued suitability for receiving combination nivolumab\u002Fcabozantinib treatment\n  * Participants with treated brain metastases must have discontinued steroid treatment at least 14 days prior to step 2 registration\n  * Participants must not have received investigational agents or monoclonal antibodies (except Food and Drug Administration \\[FDA\\] approved supportive care antibodies, such as denosumab) within 28 days prior to step 2 registration\n  * Participants must not have received surgery, chemotherapy, radiation therapy, biologic agents, or steroids within 14 days prior to step 2 registration\n  * Participants must not have received administration of a live, attenuated vaccine within 30 days prior to step 2 registration. Note: Participants may have received a messenger ribonucleic acid (mRNA) or viral vector-based coronavirus disease 2019 (COVID-19) vaccine within 30 days prior to step 2 registration\n  * Participants must not have received administration of any strong CYP3A4 inducers, such as but not limited to rifampin, carbamazepine, enzalutamide, mitotane, phenytoin and St. John's wort, within 14 days prior to step 2 registration\n  * Participants must not have received administration of any strong CYP3A4 inhibitors, such as but not limited to clarithromycin, itraconazole, ketoconazole, grapefruit juice, indinavir, nelfinavir, ritonavir, nefazodone, saquinavir, and telithromycin, within 5 times the half-life of the CYP3A inhibitor prior to step 2 registration\n  * Participants must have a history and physical examination performed within 28 days prior to step 2 registration\n  * Leukocytes \\>= 3,000\u002FuL (within 28 days prior to step 2 registration)\n  * Absolute neutrophil count \\>= 1,500\u002FuL (within 28 days prior to step 2 registration)\n  * Platelets \\>= 100,000\u002FuL (within 28 days prior to step 2 registration)\n  * Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN) or =\\\u003C 3 x ULN for participants with Gilbert's disease (within 28 days prior to step 2 registration)\n  * Aspartate aminotransferase (AST) =\\\u003C 3 x institutional ULN (within 28 days prior to step 2 registration)\n  * Alanine aminotransferase (ALT) =\\\u003C 3 x institutional ULN (within 28 days prior to step 2 registration)\n  * Urinalysis: For baseline value (no required value for eligibility)\n  * Measured (OR calculated) creatinine clearance \\>= 30 mL\u002Fmin using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to step 2 registration","ALL","18 Years",{"count":19,"type":20},150,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or squamous cell head and neck cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine how quickly patients can be divided into groups based on biomarkers in their tumors. A biomarker is a biological molecule found in the blood, other body fluids, or in tissues that is a sign of a normal or abnormal process or a sign of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. The two biomarkers that this trial is studying are \"tumor mutational burden\" and \"tumor inflammation signature.\" Another purpose of this trial is to help doctors learn if cabozantinib and nivolumab shrink or stabilize the cancer, and whether patients respond differently to the combination depending on the status of the biomarkers.",[26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50],"Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8","Locally Recurrent Head and Neck Squamous Cell Carcinoma","Locally Recurrent Hypopharyngeal Squamous Cell Carcinoma","Locally Recurrent Laryngeal Squamous Cell Carcinoma","Locally Recurrent Oral Cavity Squamous Cell Carcinoma","Locally Recurrent Oropharyngeal Squamous Cell Carcinoma","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hypopharyngeal Squamous Cell Carcinoma","Metastatic Laryngeal Squamous Cell Carcinoma","Metastatic Melanoma","Metastatic Oral Cavity Squamous Cell Carcinoma","Metastatic Oropharyngeal Squamous Cell Carcinoma","Recurrent Melanoma","Stage III Hypopharyngeal Carcinoma AJCC v8","Stage III Laryngeal Cancer AJCC v8","Stage III Lip and Oral Cavity Cancer AJCC v8","Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8","Stage IV Hypopharyngeal Carcinoma AJCC v8","Stage IV Laryngeal Cancer AJCC v8","Stage IV Lip and Oral Cavity Cancer AJCC v8","Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8","Unresectable Melanoma","RECRUITING","2026-06-25",{"date":54,"type":55},"2026-06-26","ACTUAL",{"date":57,"type":55},"2022-12-06",{"date":59,"type":20},"2027-01-01",{"name":61,"class":62},"National Cancer Institute (NCI)","NIH",223,{"id":65,"slug":66,"hasResults":11,"nctId":67,"briefTitle":68,"officialTitle":69,"acronym":70,"eligibilityCriteria":71,"healthyVolunteers":11,"sex":16,"minAge":72,"maxAge":4,"enrollmentInfo":73,"targetDuration":4,"studyType":21,"phases":75,"briefSummary":77,"conditions":78,"keywords":4,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":174,"lastUpdatePostDateStruct":175,"startDateStruct":177,"completionDateStruct":179,"leadSponsor":181,"locationsCount":184},"100459958","phase-1-personalized-neoantigen-peptide-based-vaccine-in-combination-with-pembrolizumab-for-treatment-of-advanced-solid-tumors-100459958","NCT05269381","Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors","A Phase I\u002FII Study of Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab in Advanced Solid Tumors (PNeoVCA)","PNeoVCA","Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.\n\nPHASE I PRE-REGISTRATION, ALL:\n\n* Willing to provide tissue specimens per protocol\n\n  * NOTE: includes fresh tissue specimen at pre-registration for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo Institutional Review Board (IRB) protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration.\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n* Willing to provide blood specimens for research\n* Negative pregnancy test =\\\u003C 7 days prior to pre-registration for persons of childbearing potential. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1\n* Anticipated life expectancy \\> 6 months\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).\n* The following lab values obtained =\\\u003C 28 days prior to pre-registration:\n\n  * Hemoglobin \\>= 9.0 g\u002FdL (Must be \\>= 7 days after most recent transfusion)\n  * Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3 or \\>= 1.5 X 10\\^9\u002FL\n  * Platelet count \\>= 100,000\u002Fmm\\^3 or \\>= 100 X 10\\^9\u002FL (Must be \\>=7 days after most recent transfusion)\n  * Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN)\n  * Aspartate transaminase (AST) and alanine transaminase (ALT) =\\\u003C 3 x ULN or =\\\u003C 5 x ULN with liver metastases\n  * Creatinine =\\\u003C 1.5 x ULN OR calculated creatinine clearance must be \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n  * International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy\n\nPHASE I REGISTRATION, ALL:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood and tissue specimens for research\n* Willing to return to enrolling institution for follow-up\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have also received and progressed on at least one line of prior FDA-approved targeted therapy\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only\n\n  * NOTE: If urine test cannot be confirmed negative, serum pregnancy test will be required\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (for laboratory toxicity see specified limits for inclusion) or NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nPHASE II PRE-SCREENING COHORT 3 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of adenocarcinoma of the breast with estrogen receptor (ER) \\\u003C 10%, progesterone receptor (PR) \\\u003C 10%, and HER2 negative based on current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guideline\n* Stage I-III based on 7th edition of TNM staging system from American Joint Committee on Cancer (AJCC)\n* Evidence of residual disease \\>= 1 cm after neoadjuvant pembrolizumab-based chemotherapy on imaging for patients who have not had surgery\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-SCREENING COHORT 4 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of lung NSCLC\n* No actionable EGFR mutations and ALK fusions\n* Stage II or stage III based on AJCC 8th\n* Tumor \\>= 2 cm on pre-surgery evaluation imaging (residual disease \\>= 2 cm after neoadjuvant therapy on pre-surgery evaluation imaging in patient who receives neoadjuvant therapy) for patients who have not had surgery. Patients with or without neoadjuvant chemotherapy or immunotherapy are allowed\n* Provide written informed consent\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-REGISTRATION COHORT 3 (TNBC) ONLY:\n\n* Histologically confirmed residual cancer burden 2 and 3 in surgical specimens\n\nPHASE II PRE-REGISTRATION COHORT 4 (NSCLC) ONLY:\n\n* Tumor without complete pathologic response is confirmed in pathology\n* Willing to proceed with surgery and provide tissue specimens for complete exome and transcriptome sequencing\n\n  * NOTE: Patients who had sequencing under certain Mayo IRB protocols and neoantigens identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration\n* Negative pregnancy test ≤7 days prior to pre-registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* ECOG PS of 0 or 1\n* Anticipated life expectancy \\> 6 months\n\nPHASE II REGISTRATION:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Patients will receive \\>= 2 additional cycles of maintenance pembrolizumab\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood specimens for research\n* Willing to return to enrolling institution for follow-up\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nExclusion Criteria\n\nALL PHASES:\n\n* Any of the following because study involves investigational agent whose genotoxic, mutagenic and teratogenic effects on developing fetus and newborn are unknown:\n\n  * Pregnant person\n  * Nursing person unwilling to stop breast feeding\n  * Person of childbearing potential unwilling to employ adequate contraception from registration through 6 months after final vaccine cycle\n* Co-morbid systemic illnesses or other severe concurrent disease which, in judgment of investigator, would make patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and toxicity of prescribed regimens\n* History of myocardial infarction =\\\u003C 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.\n* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy\n\nPHASE I PRE-REGISTRATION:\n\n* Acute, reversible effect(s) of prior therapy not recovered to baseline regardless of interval since last treatment\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Psychiatric illness\u002Fsocial situations\n  * Congestive heart failure with New York Heart Association (NYHA) class III or IV moderate to severe objective evidence of cardiovascular disease\n  * Stroke =\\\u003C 3 months prior to pre-registration\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Receiving any other investigational agent which would be considered treatment for primary neoplasm, except pembrolizumab\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* History of active autoimmune disease (AD) that required systemic treatment in =\\\u003C 30 days (i.e., use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with celiac disease controlled with diet modification are not excluded PHASE I REGISTRATION\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major Surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n  * Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= Grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent permitted in absence of active AD\n* Evidence of leptomeningeal disease or central nervous system metastases that are untreated, symptomatic, or require steroids \\>10 mg daily prednisone equivalent\n\n  * NOTE: Patients with history of stable treated brain metastases are eligible. Stable treated metastases defined as no evidence of progression for ≥4 weeks on brain imaging (MRI or CT scan)\n\nPHASE II PRE-SCREENING:\n\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-screening\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-screening\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n\nPHASE II PRE-REGISTRATION\n\n* Uncontrolled illness including, but not limited to:\n\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If history of prior malignancy, must not be receiving other specific treatment for cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n* Patients will also be excluded based on tissue\u002Fribonucleic acid (RNA)\u002Fdeoxyribonucleic acid (DNA) quality and quantity. If any of the following quality and quantity thresholds are not met, patient will be excluded: (1) tumor tissue cellularity equal to or greater than 30%; (2) there are \\>= 2 cores with passing cellularity; (3) \\>= 30% of tumor RNA with fragment sizes are \\>= 200 base pairs (DV200 \\>= 30); (4) \\\u003C 10% of DNA fragments are smaller than 1 kb; and (5) sufficient amount of both DNA (blood and tumor) and RNA (tumor) for exome sequencing and whole transcriptome sequencing (RNAseq) according to Mayo sequencing core. (Kits and technologies change overtime, so these are not fixed numbers.)\n\nPHASE II REGISTRATION\n\n* Evidence of metastatic disease or recurrence\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n\n    * NOTE: Continuation of pembrolizumab per standard of care is allowed\n    * NOTE: Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= grade 3 TEAE to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy), or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Requirement for systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent are permitted in","16 Years",{"count":74,"type":20},132,[76,23],"PHASE1","This phase I\u002FII trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.",[79,80,81,82,83,26,84,85,86,28,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,35,117,118,119,38,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,50,164,165,166,167,168,169,170,171,172,173],"Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IIIA Breast Cancer AJCC v8","Anatomic Stage IIIB Breast Cancer AJCC v8","Anatomic Stage IIIC Breast Cancer AJCC v8","Anatomic Stage IV Breast Cancer AJCC v8","Clinical Stage III Gastric Cancer AJCC v8","Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage III Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Gastric Cancer AJCC v8","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IV Merkel Cell Carcinoma AJCC v8","Clinical Stage IVA Gastric Cancer AJCC v8","Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IVB Gastric Cancer AJCC v8","Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Locally Advanced Cervical Carcinoma","Locally Advanced Endometrial Carcinoma","Locally Advanced Gastric Adenocarcinoma","Locally Advanced Gastroesophageal Junction Adenocarcinoma","Locally Advanced Head and Neck Squamous Cell Carcinoma","Locally Advanced Hepatocellular Carcinoma","Locally Advanced Lung Non-Small Cell Carcinoma","Locally Advanced Malignant Solid Neoplasm","Locally Advanced Melanoma","Locally Advanced Merkel Cell Carcinoma","Locally Advanced Renal Cell Carcinoma","Locally Advanced Skin Squamous Cell Carcinoma","Locally Advanced Triple-Negative Breast Carcinoma","Locally Advanced Unresectable Breast Carcinoma","Locally Advanced Unresectable Cervical Carcinoma","Locally Advanced Unresectable Gastric Adenocarcinoma","Locally Advanced Unresectable Gastroesophageal Junction Adenocarcinoma","Locally Advanced Unresectable Renal Cell Carcinoma","Locally Advanced Urothelial Carcinoma","Metastatic Cervical Carcinoma","Metastatic Endometrial Carcinoma","Metastatic Gastric Adenocarcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Malignant Solid Neoplasm","Metastatic Merkel Cell Carcinoma","Metastatic Renal Cell Carcinoma","Metastatic Skin Squamous Cell Carcinoma","Metastatic Triple-Negative Breast Carcinoma","Metastatic Urothelial Carcinoma","Skin Squamous Cell Carcinoma","Stage III Cervical Cancer AJCC v8","Stage III Hepatocellular Carcinoma AJCC v8","Stage III Lung Cancer AJCC v8","Stage III Renal Cell Cancer AJCC v8","Stage IIIA Cervical Cancer AJCC v8","Stage IIIA Hepatocellular Carcinoma AJCC v8","Stage IIIA Lung Cancer AJCC v8","Stage IIIA Uterine Corpus Cancer AJCC v8","Stage IIIB Cervical Cancer AJCC v8","Stage IIIB Hepatocellular Carcinoma AJCC v8","Stage IIIB Lung Cancer AJCC v8","Stage IIIB Uterine Corpus Cancer AJCC v8","Stage IIIC Lung Cancer AJCC v8","Stage IIIC Uterine Corpus Cancer AJCC v8","Stage IIIC1 Uterine Corpus Cancer AJCC v8","Stage IIIC2 Uterine Corpus Cancer AJCC v8","Stage IV Cervical Cancer AJCC v8","Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IV Lung Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","Stage IVA Cervical Cancer AJCC v8","Stage IVA Hepatocellular Carcinoma AJCC v8","Stage IVA Lung Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Cervical Cancer AJCC v8","Stage IVB Hepatocellular Carcinoma AJCC v8","Stage IVB Lung Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8","Triple-Negative Breast Carcinoma","Unresectable Cervical Carcinoma","Unresectable Endometrial Carcinoma","Unresectable Gastric Adenocarcinoma","Unresectable Gastroesophageal Junction Adenocarcinoma","Unresectable Head and Neck Squamous Cell Carcinoma","Unresectable Hepatocellular Carcinoma","Unresectable Lung Non-Small Cell Carcinoma","Unresectable Malignant Solid Neoplasm","Unresectable Merkel Cell Carcinoma","Unresectable Renal Cell Carcinoma","Unresectable Skin Squamous Cell Carcinoma","Unresectable Triple-Negative Breast Carcinoma","Unresectable Urothelial Carcinoma","Breast Adenocarcinoma","Stage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","2026-06-18",{"date":176,"type":55},"2026-06-23",{"date":178,"type":55},"2022-03-31",{"date":180,"type":20},"2028-03-31",{"name":182,"class":183},"Mayo Clinic","OTHER",1,{"id":186,"slug":187,"hasResults":11,"nctId":188,"briefTitle":189,"officialTitle":190,"acronym":4,"eligibilityCriteria":191,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":192,"targetDuration":4,"studyType":21,"phases":194,"briefSummary":196,"conditions":197,"keywords":4,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":207,"lastUpdatePostDateStruct":208,"startDateStruct":210,"completionDateStruct":212,"leadSponsor":214,"locationsCount":184},"100624088","phase-4-morning-versus-afternoon-administration-of-immunotherapy-for-the-treatment-of-advanced-or-metastatic-solid-tumors-the-knight-shift-study-100624088","NCT07405086","Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study","Knight Cancer Institute Study of Histology-Agnostic Immunotherapy With Focus on Timing: - Knight SHIFT - A Prospective, Multi-Histology Pragmatic Study","Inclusion Criteria:\n\n* Must provide written informed consent before any study-specific procedures or interventions are performed\n* Aged ≥ 18 years\n* Histologically confirmed advanced\u002Fmetastatic solid tumor as follows:\n\n  * Non small cell lung cancer (NSCLC) (driver-negative, immune checkpoint inhibitor \\[ICI\\]-eligible)\n  * Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) (platinum-eligible),\n  * Renal cell carcinoma (RCC)\n  * Biliary-tract cancer (BTC)\n  * Hepatocellular carcinoma (HCC)\n  * Melanoma\n* Planned to receive a Food and Drug Administration (FDA)-approved immune check point inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) regimen for the treatment of their malignancy\n* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n\nExclusion Criteria:\n\n* Prior ICI-based regimen for treatment of cancer\n* Current or prior use of immunosuppressive medication within 28 days before planned standard-of-care immunotherapy infusion, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not exceeding 10 mg\u002Fday of prednisone (or equivalent corticosteroid)\n* Uncontrolled autoimmune disease requiring immunosuppression\n* Active, uncontrolled central nervous system (CNS) metastases",{"count":193,"type":20},160,[195],"PHASE4","This phase IV trial is evaluating whether morning versus afternoon administration of standard of care immunotherapy impacts its effectiveness in treating patients with solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Circadian rhythm refers to the internal biological clock in which various processes in the body, including immune cell activity, are controlled by the time of day. Exactly how this works is not fully understood, and the researchers want to see if circadian rhythm control of the immune system can influence response to immunotherapy based on whether it is given in the morning (before 11:00 am) or afternoon (12:00pm). The time of day that immunotherapy is given (morning versus afternoon) may impact the effectiveness in treating patients with advanced or metastatic solid tumors.",[198,199,200,201,202,203,204,205,35,117,118,119,38,121,206,127,128,129,144,145,146],"Advanced Biliary Tract Carcinoma","Advanced Head and Neck Squamous Cell Carcinoma","Advanced Hepatocellular Carcinoma","Advanced Lung Non-Small Cell Carcinoma","Advanced Malignant Solid Neoplasm","Advanced Melanoma","Advanced Renal Cell Carcinoma","Metastatic Biliary Tract Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","2026-06-10",{"date":209,"type":55},"2026-06-12",{"date":211,"type":55},"2026-06-08",{"date":213,"type":20},"2028-12-31",{"name":215,"class":183},"OHSU Knight Cancer Institute",{"id":217,"slug":218,"hasResults":11,"nctId":219,"briefTitle":220,"officialTitle":221,"acronym":4,"eligibilityCriteria":222,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":223,"targetDuration":4,"studyType":21,"phases":225,"briefSummary":227,"conditions":228,"keywords":4,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":207,"lastUpdatePostDateStruct":239,"startDateStruct":241,"completionDateStruct":243,"leadSponsor":245,"locationsCount":246},"100561410","phase-3-testing-the-addition-of-anti-cancer-drug-cetuximab-to-standard-of-care-treatment-pembrolizumab-for-returning-or-spreading-head-and-neck-cancer-after-previous-treatment-100561410","NCT06589804","Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment","Randomized Phase III Trial of Pembrolizumab vs. Pembrolizumab\u002FCetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma With Platinum Refractory Disease","Inclusion Criteria:\n\n* Histologically confirmed diagnosis head and neck squamous cell carcinomas (HNSCC).\n* Previously untreated for recurrent and\u002For metastatic disease incurable by local therapies.\n* Primary tumor location of oral cavity, oropharynx, larynx, or hypopharynx.\n\n  * Note: Other primary tumor sites of HNSCC, including nasopharynx primary tumor are not eligible. Unknown primary tumors may be eligible and can be enrolled at the discretion of the treatment team with approval by the study chair.\n* Measurable disease.\n* Must have platinum-refractory disease defined as disease progression during or ≤ 29 weeks after completion of definitive therapy (chemoradiation therapy) or adjuvant (post-operative) therapy.\n* Patient must have a combined positive score PD-L1 positive (CPS \\>\u002F= 1) tumor.\n* Any radiation therapy must be completed \\>= 10 days prior to registration.\n* Patients should not have received any prior treatment in the recurrent or metastatic setting.\n* Prior therapy with neoadjuvant or induction anti PD-1\u002FPD-L1 monoclonal antibody or cetuximab in the curative setting is allowed if last treatment dose was \\>= 26 weeks prior to registration without evidence of disease progression during that treatment period.\n* Patient has not received a live vaccine within 30 days prior to registration.\n* Patient does not have a history of any contraindication or has a severe hypersensitivity to any component of pembrolizumab or cetuximab (≥ grade 3).\n* Patient has not received chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to registration.\n* Patient with oropharyngeal cancer only must have negative results from testing of human papillomavirus (HPV) status defined as p16 immunohistochemistry (IHC) and\u002For HPV in situ hybridization (ISH).\n\n  * Note: A Clinical Laboratory Improvement Act (CLIA) certified circulating tumor HPV deoxyribonucleic acid (ctHPVDNA) assay can be used if tissue sample is not available.\n* Age ≥ 18 years.\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.\n* Absolute neutrophil count (ANC) ≥ 1,500\u002Fmm\\^3.\n* Platelet count ≥ 100,000\u002Fmm\\^3.\n* Hemoglobin (Hgb) ≥ 9 g\u002FdL (if \\\u003C 9 g\u002FdL, then transfusions are acceptable to increase hemoglobin above 9 g\u002FdL).\n* Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance ≥ 30 mL\u002Fmin using the Cockcroft-Gault formula for participant with creatinine levels \\> 1.5 x institutional ULN.\n* Total bilirubin ≤ 1.5 x ULN OR direct bilirubin \\\u003C ULN for participant with total bilirubin \\> 1.5 x institutional ULN.\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \\[SGPT\\]) ≤ 3.0 x ULN unless liver metastases are present in which case \\\u003C 5.0 x ULN.\n* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.\n\n  * Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 7 days prior to registration is required.\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen should be included.\n* For treated\u002Fstable brain metastases: Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.\n\n  * Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.\n* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial.\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.\n* Patients does not have a history of active myocarditis.\n* Patients does not have a history of any form of pneumonitis or diffuse idiopathic or immune mediated interstitial pulmonary disease.\n* Patient does not have a history of solid organ transplantation.",{"count":224,"type":20},158,[226],"PHASE3","This phase III trial compares the effect of adding cetuximab to pembrolizumab versus pembrolizumab alone in treating patients with head and neck squamous cell carcinoma (HNSCC) that has come back after a period of improvement (recurrent) and\u002For that has spread from where it first started (primary site) to other places in the body (metastatic). Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of tumor cells. This may help keep tumor cells from growing. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving cetuximab and pembrolizumab together may be more effective at treating patients with recurrent and\u002For metastatic HNSCC than pembrolizumab alone.",[35,36,37,39,40,206,229,230,231,232,233,234,235,236,237,238,173,46,47,48,49],"Recurrent Hypopharyngeal Squamous Cell Carcinoma","Recurrent Laryngeal Squamous Cell Carcinoma","Recurrent Neck Squamous Cell Carcinoma of Unknown Primary","Recurrent Oral Cavity Squamous Cell Carcinoma","Recurrent Oropharyngeal Squamous Cell Carcinoma","Refractory Head and Neck Squamous Cell Carcinoma","Refractory Hypopharyngeal Squamous Cell Carcinoma","Refractory Laryngeal Squamous Cell Carcinoma","Refractory Oral Cavity Squamous Cell Carcinoma","Refractory Oropharyngeal Squamous Cell Carcinoma",{"date":240,"type":55},"2026-06-11",{"date":242,"type":55},"2025-03-27",{"date":244,"type":20},"2029-11-30",{"name":61,"class":62},177,{"id":248,"slug":249,"hasResults":11,"nctId":250,"briefTitle":251,"officialTitle":252,"acronym":4,"eligibilityCriteria":253,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":254,"targetDuration":4,"studyType":21,"phases":256,"briefSummary":257,"conditions":258,"keywords":264,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":207,"lastUpdatePostDateStruct":265,"startDateStruct":266,"completionDateStruct":268,"leadSponsor":270,"locationsCount":272},"100534468","phase-2-pd-l1-t-hank-nai-il-15sa-and-cetuximab-for-recurrent-metastatic-hnscc-100534468","NCT06239220","PD-L1 t-haNK, NAI IL-15sa and Cetuximab for Recurrent, Metastatic HNSCC","A Phase 2 Trial of PD-L1 t-haNK, NAI IL-15 Superagonist (Anktiva), and Cetuximab for Immunotherapy-treated Patients With Recurrent, Metastatic HNSCC (QUILT-505)","Inclusion Criteria:\n\n* Participants must have an existing histologically confirmed diagnosis of head and neck squamous cell carcinoma (HNSCC) with evidence of recurrent, metastatic (R\u002FM) or locoregionally advanced, incurable or unresectable disease from any mucosal subsite including oral cavity, oropharynx, larynx, hypopharynx, nasal cavity, and the paranasal sinuses.\n* Participants must have at least one RECIST v1.1 measurable lesion, as defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) ≥ 1 cm with CT scans or MR imaging.\n* Must have had at least 1, but no more than 2, prior lines of prior systemic therapy for R\u002FM HNSCC; one of these lines should have included anti-PD-1\u002FL1 therapy.\n\n  * a.Platinum-based therapy as part of definitive\u002Fadjuvant or curative-intent treatment can count as 1 prior line of therapy if the subject progressed within 6 months of receiving therapy.\n  * b. At least 2 weeks must have elapsed since the end of prior chemotherapy, biological agents (2 weeks for anti-cancer monoclonal antibody containing regimens) or any investigational drug product, with adequate recovery of treatment-related toxicity to NCI CTCAE v5 grade ≤1 (or tolerable grade 2) or back to baseline (except for alopecia or peripheral neuropathy).\n* Be ≥18 years of age on the day of signing informed consent.\n* Must provide prior documentation on tumor PD-L1 expression status and HPV status (for oropharyngeal cancer cases), if available from the medical record.\n* Have a performance status of 0 or 1 on the ECOG Performance Scale (see Appendix A).\n* Participants must have adequate organ and marrow function as defined below (within 14 days prior to study registration):\n\n  * a. ANC ≥1,000\u002FmcL\n  * b. Hemoglobin ≥9 g\u002FdL\n  * c. Platelets ≥100,000\u002FmcL\n  * d. Total bilirubin ≤ upper limit of normal (ULN)\n  * e. AST(SGOT)\u002FALT(SGPT) ≤2.5x institutional ULN (or ≤1.5x institutional ULN if concomitant with alkaline phosphatase \\>2.5x institutional ULN) or ≤5x ULN for those with liver metastases\n  * g. Serum creatinine ≤1.5x ULN or creatinine clearance ≥60 mL\u002Fmin\u002F1.73 m2 for participants with creatinine levels above 1.5x ULN\n* Baseline tumor measurements must be documented from imaging within 28 days prior to study registration.\n* Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 7 days of study registration. Female subjects should not become pregnant or nurse a baby during the study and through 120 days after the last dose of study drugs. Male subjects should use a condom as a contraceptive during the study and through 120 days after the last dose of study drugs.\n\nSperm donation is discouraged for up to 6 months after the last dose of study drug.\n\n-Be willing and able to provide written informed consent for the trial.\n\nExclusion Criteria\n\n* Have been previously treated with 3 or more lines of systemic therapy for R\u002FM HNSCC.\n* Have received radiation therapy (RT) within 10 days of starting protocol therapy.\n* Solid organ transplant (allograft) recipients.\n* Participant has known active central nervous system (CNS) metastases and\u002For carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging and off systemic steroids for at least 3 weeks prior to study registration) and have no evidence of new or enlarging brain metastases.\n* A history of significant autoimmune disease as judged by the treating investigator and on active therapy including prednisone ≥10 mg daily dose equivalent of corticosteroids.\n* Uncontrolled intercurrent illness including but not limited to ongoing or active infection; evidence of symptomatic congestive heart failure, unstable angina pectoris, stroke, or ventricular arrhythmia within 6 months of enrollment.\n* Has a known additional malignancy that is progressing or requires active treatment. Exceptions might include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.\n* Any known positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., hepatitis B surface antigen (HBsAg, Australia antigen) positive, or hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative). Patients with HIV are eligible if their plasma HIV viral load is undetectable at baseline on antiretroviral therapy.\n* Subjects who are pregnant, or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. Breastfeeding should be discontinued if the mother is treated on this protocol. Women who could potentially become pregnant while undergoing treatment on this protocol must be willing to use 2 methods of contraception.",{"count":255,"type":20},25,[23],"The purpose of this research study is to test the safety and efficacy of the combination of PD-L1 t-haNK (modified immune cells), NAI (a manufactured protein that stimulates the immune system), and cetuximab (a targeted antibody) in treating advanced head and neck cancer.\n\nThe names of the therapies involved in this study are:\n\n* PD-L1 t-haNK cell therapy (a NK cell therapy infusion)\n* NAI (a type of recombinant human superagonist)\n* Cetuximab (a type of antibody)",[259,260,261,262,263,206],"Head and Neck Cancer","Head and Neck Squamous Cell Carcinoma","Metastatic Head and Neck Cancer","Recurrent Head and Neck Cancer","Metastatic Head-and-neck Squamous-cell Carcinoma",[259,260,261,262,263,206],{"date":240,"type":55},{"date":267,"type":55},"2024-02-16",{"date":269,"type":20},"2027-01-31",{"name":271,"class":183},"Glenn J. Hanna",2,{"id":274,"slug":275,"hasResults":11,"nctId":276,"briefTitle":277,"officialTitle":278,"acronym":4,"eligibilityCriteria":279,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":280,"targetDuration":4,"studyType":21,"phases":282,"briefSummary":283,"conditions":284,"keywords":4,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":305,"lastUpdatePostDateStruct":306,"startDateStruct":308,"completionDateStruct":310,"leadSponsor":312,"locationsCount":184},"100536473","phase-2-comparison-of-in-home-versus-in-clinic-administration-of-subcutaneous-nivolumab-through-cancer-care-connected-access-and-remote-expertise-beyond-walls-ccbw-program-100536473","NCT06265285","Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program","MC230716 Pilot Single-Arm, Pragmatic Trial Of In-Home Versus In-Clinic Subcutaneous Nivolumab Administration Through Cancer CARE (Connected Access And Remote Expertise) Beyond Walls (CCBW) Program","Inclusion Criteria:\n\n* Age ≥ 18 years\n* Histologically confirmed malignancies for which treatment with intravenous nivolumab is currently Food and Drug Administration (FDA) approved and who are recommended to initiate a new treatment regimen with single agent intravenous (IV) nivolumab by their treating oncologist for any of the indications outlined below and who are willing to switch to subcutaneous nivolumab. Additionally, patients who are currently receiving single-agent IV nivolumab are eligible, provided they transition to subcutaneous nivolumab on-study, with their first subcutaneous (subQ) dose administered on cycle 1, day 1 of the study.\n\n  * Single agent nivolumab administered in the adjuvant setting for one of the following indications:\n\n    * Completely resected stage IIB\u002FC, III or IV melanoma\n    * Urothelial carcinoma status post radical resection and have a high risk of recurrence\n    * Completely resected esophageal or gastroesophageal junction carcinoma with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT)\n  * Single agent nivolumab for advanced\u002Fmetastatic cancer for one or more of the following indications:\n\n    * Renal cell carcinoma (RCC) patients who have received prior anti-angiogenic therapy\n    * Non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy (Note: patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab)\n    * Unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy\n    * Unresectable or metastatic cutaneous melanoma\n    * Locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy\n    * Unresectable or metastatic urothelial carcinoma, as first-line treatment in combination with cisplatin and gemcitabine.\n\n      * Subcutaneous nivolumab to be initiated as monotherapy following six cycles of cisplatin + gemcitabine\n    * Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy\n    * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan\n  * Patients transitioning to maintenance nivolumab and who are willing to switch to subcutaneous nivolumab after completion of Ipilimumab and nivolumab combination therapy for one or more of the indications listed below (Note: patients who discontinue ipilimumab for immune-related toxicities, but are deemed to be eligible to continue on single agent nivolumab maintenance by their treating oncologist are eligible):\n\n    * First-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC)\n    * Unresectable or metastatic cutaneous melanoma\n    * Hepatocellular carcinoma (HCC) previously treated with sorafenib\n    * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan\n  * Single agent nivolumab administered in the adjuvant setting following neoadjuvant nivolumab with platinum doublet chemotherapy for patients with resectable (tumors ≥ 4 cm and\u002For node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements\n* Patients have recovered from the effects of any previous chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, and\u002For surgery (i.e., residual toxicity no worse than grade 1 \\[grade 2 treatment-associated peripheral neuropathy, grade 2 fatigue and\u002For any grade of alopecia are acceptable assuming all other inclusion criteria are met\\]) before registration\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1\n* Aspartate transaminase (AST) values ≤ 3 × the upper limit of normal (ULN). For patients with documented baseline liver metastasis, the following limits will apply: 5 × ULN for transaminase\n* Alanine transaminase (ALT) values ≤ 3 x the upper limit of normal (ULN). For patients with documented baseline liver metastasis, the following limits will apply: 5 x ULN for transaminase\n* Serum total bilirubin values of ≤ 1.5 x ULN ( ≤ 2 x ULN for patients with known Gilbert's syndrome). For patients with documented baseline liver metastasis, the following limits will apply: 2 x ULN for bilirubin\n* Absolute neutrophil count (ANC) of ≥ 1500\u002FμL\n* Platelet count of ≥ 100,000\u002FμL\n* Hemoglobin of ≥ 9 g\u002FdL (patients may be transfused to this level, if necessary, but transfusion must occur \\> 1 week prior to registration)\n* Serum creatinine ≤ 2.0 x the ULN for the reference laboratory or a calculated creatinine clearance of ≥ 30 mL\u002Fmin by the Cockcroft-Gault Equation measured ≤ 7 days prior to registration\n* Patients are residing ≤ 35 miles of clinic (hub) or within the area serviced by supplier and paramedic network\n* Residence has Wi-Fi to enable a reliable connection with the remote command center\n* Patients have signed Informed Consent Form (ICF)\n* Patients are willing and able to comply with the study protocol in the investigator's judgment\n* Patients are able and willing to complete study questionnaire(s) by themselves or with assistance\n* Women of childbearing potential (WOCBP) must:\n\n  * Have a negative pregnancy test (serum or urine) ≤ 3 days before the first dose of study drug\n  * Be agreeable to use a contraceptive method that is highly effective during the intervention period and for at least 5 months after the last dose and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the same time period\n\nExclusion Criteria:\n\n* Patients receiving any other investigational or standard of care agent which would be considered as a treatment for the primary neoplasm and is not part of the eligible treatment regimen\n* Patients requiring 24\u002F7 assistance with activities of daily living (ADLs)\n* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Cardiac arrhythmia\n  * Myocardial infarction ≤ 6 months\n  * Wound healing disorder\n  * Psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Patients with any severe infection ≤ 4 weeks prior to registration including, but not limited to, hospitalization for complications of infections\n* Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with celiac disease controlled with diet modification are not excluded\n* Patients with a condition requiring systemic treatment with either corticosteroids ( \\> 10 mg daily prednisone equivalent) ≤ 14 days or other immunosuppressive medications ≤ 30 days prior to registration. Inhaled or topical steroids, and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease\n* Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active ≤ 2 years prior to registration (i.e., participants with a history of prior malignancy are eligible if treatment was completed at least 2 years before randomization\u002Ftreatment assignment and the patient has no evidence of disease). Participants with history of prior early stage basal\u002Fsquamous cell skin cancer or non-invasive or in situ cancers that have undergone definitive treatment at any time are also eligible\n* Patients have undergone prior solid organ and\u002For non-autologous hematopoietic stem cell or bone marrow transplant\n* Patients with active brain metastases or leptomeningeal metastases, aside from the exceptions below. Participants with brain metastases are eligible if they are:\n\n  * Asymptomatic\n  * Have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the central nervous system \\[CNS\\] treatment), and\n  * There is no MRI evidence of progression for at least 4 weeks after CNS directed therapy is complete and ≤ 28 days prior to registration\n  * In addition, participants must have been either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to registration\n* Participants with brain disease treated with whole brain radiation\n* Anticipation of the need for major surgery during the course of study treatment\n* Participants who are pregnant or breastfeeding\n* Treatment with any live attenuated vaccines ≤ 30 days of registration (vaccines that are not live attenuated are allowed, including COVID-19 vaccine)\n* Known human deficiency virus (HIV) positive with an AIDS defining opportunistic infection within the last year, or a current CD4 count \\\u003C 350 cells\u002FuL, aside from the exceptions below. Participants with HIV are eligible if:\n\n  * They have received antiviral therapy (ART) for at least 4 weeks prior to treatment assignment as clinically indicated while enrolled in the study\n  * They continue on ART as clinically indicated while enrolled on study\n  * CD4 counts and viral load are monitored per standard of care by a local healthcare provider\n* History of allergy or hypersensitivity to study drug components\n* Any positive test result for hepatitis B virus (HBV) indicating presence of virus (e.g., hepatitis B surface antigen \\[HBsAg, Australia antigen\\]) positive\n* Any positive test result for hepatitis C virus (HCV) indicating presence of active viral replication (detectable HCV-ribonucleic acid \\[RNA\\]). Note: Participants with positive HCV antibody and an undetectable HCV RNA are eligible to enroll",{"count":281,"type":20},50,[23],"This phase II trial compares the impact of subcutaneous (SC) nivolumab given in an in-home setting to an in-clinic setting on cancer care and quality of life. Currently, most drug-related cancer care is conducted in clinic type centers or hospitals which may isolate patients from family, friends and familiar surroundings for many hours per day. This separation adds to the physical, emotional, social, and financial burden for patients and their families. Traveling to and from medical facilities costs time, money, and effort and can be a disadvantage to patients living in rural areas, those with low incomes or poor access to transport. Studies have shown that cancer patients often feel more comfortable and secure being cared for in their own home environments. SC nivolumab in-home treatment may be safe, tolerable and\u002For effective when compared to in-clinic treatment and may reduce the burden of cancer and improve the quality of life in cancer patients.",[285,204,286,287,288,26,289,28,290,291,292,293,112,294,295,296,297,298,35,124,299,206,300,129,301,143,146,302,303,304,168],"Advanced Esophageal Squamous Cell Carcinoma","Clinical Stage II Esophageal Squamous Cell Carcinoma AJCC v8","Clinical Stage IIB Cutaneous Melanoma AJCC v8","Clinical Stage IIC Cutaneous Melanoma AJCC v8","Clinical Stage III Esophageal Squamous Cell Carcinoma AJCC v8","Clinical Stage IV Esophageal Squamous Cell Carcinoma AJCC v8","Esophageal Carcinoma","Gastroesophageal Junction Adenocarcinoma","Hepatocellular Carcinoma","Lung Non-Small Cell Carcinoma","Malignant Solid Neoplasm","Metastatic Colorectal Carcinoma","Metastatic Cutaneous Melanoma","Metastatic Esophageal Squamous Cell Carcinoma","Recurrent Esophageal Squamous Cell Carcinoma","Renal Cell Carcinoma","Stage IV Colorectal Cancer AJCC v8","Unresectable Cutaneous Melanoma","Unresectable Esophageal Squamous Cell Carcinoma","Urothelial Carcinoma","2026-06-05",{"date":307,"type":55},"2026-06-09",{"date":309,"type":55},"2024-04-30",{"date":311,"type":20},"2026-12-31",{"name":182,"class":183},{"id":314,"slug":315,"hasResults":11,"nctId":316,"briefTitle":317,"officialTitle":317,"acronym":318,"eligibilityCriteria":319,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":320,"targetDuration":4,"studyType":21,"phases":322,"briefSummary":323,"conditions":324,"keywords":326,"overallStatus":331,"whyStopped":4,"lastUpdateSubmitDate":332,"lastUpdatePostDateStruct":333,"startDateStruct":334,"completionDateStruct":336,"leadSponsor":338,"locationsCount":4},"100643662","phase-4-pharmacokinetic-study-of-pembrolizumab-and-its-impact-on-immunity-and-the-tumor-microenvironment-which-may-explain-the-efficacy-of-post-immunotherapy-chemotherapy-100643662","NCT07633613","Pharmacokinetic Study of Pembrolizumab and Its Impact on Immunity and the Tumor Microenvironment, Which May Explain the Efficacy of Post-immunotherapy Chemotherapy.","CPI","Inclusion Criteria:\n\n\\- Patients over 18 years of age\n\n\\- Patients diagnosed with :\n\n1. Non-small cell lung cancer (NSCLC), including adenocarcinoma and squamous cell carcinoma.\n2. Head and neck squamous cell carcinoma, p16-negative for oropharyngeal tumors.\n\n   * Recurrent and\u002For metastatic tumor not amenable to curative locoregional treatment.\n   * Disease progression under Pembrolizumab immunotherapy, administered at the standard dose of 200 mg every 3 weeks, as first-line treatment for metastatic disease, regardless of the number of cycles received, either as monotherapy or in combination with chemotherapy, as defined below:\n\n     • For pulmonary adenocarcinomas: i. First-line treatment with Pembrolizumab in combination with a platinum agent (Carboplatin or Cisplatin) and Pemetrexed\n\n   ii. Maintenance therapy with Pembrolizumab, with or without Pemetrexed.\n\n   • For pulmonary squamous cell carcinomas: i. First-line treatment with Pembrolizumab in combination with a platinum agent (Carboplatin) and Paclitaxel\n\n   +\u002F- ii. Maintenance therapy with Pembrolizumab alone.\n\n   • For head and neck squamous cell carcinomas : i. First-line treatment with Pembrolizumab in combination with a platinum agent (Carboplatin or Cisplatin) ± 5-Fluorouracil (5-FU) or Paclitaxel\n\n   +\u002F- ii. Maintenance therapy with Pembrolizumab alone.\n   * Eligibility for salvage chemotherapy within standard care:\n\n     • For pulmonary adenocarcinomas: weekly Paclitaxel, with or without Bevacizumab.\n     * For pulmonary squamous cell carcinomas: Gemcitabine monotherapy.\n     * For head and neck squamous cell carcinomas: weekly Paclitaxel and\u002For Cetuximab. Standard salvage chemotherapy may be initiated between Day 18 and Day 35 following the last Pembrolizumab injection, at standard doses.\n   * Measurable disease according to RECIST 1.1 criteria.\n   * Performance status (PS) 0 to 2.\n   * Baseline laboratory results meeting the usual criteria permitting initiation of salvage chemotherapy.\n   * Patients who has voluntarily agreed to participate in the study (including additional blood sampling) and has signed the informed consent form.\n   * For the subpopulation with accessible tissue biopsy:\n\n     * Patient agrees to undergo biopsy,\n     * INR \\\u003C 1.5, Platelets \\> 50000\u002FμL.\n   * Patients covered by a social security health insurance scheme.\n\n   Exclusion Criteria:\n   * History of cancer, except for cancers in complete remission for more than 3 years, fully resected cutaneous basal cell carcinomas, or treated carcinoma in situ or cervical intraepithelial neoplasia (in situ cervical epithelioma),\n   * Patients participating in another clinical trial for which an exclusion period is specified,\n   * Minor patients,\n   * For the subpopulation with accessible tissue biopsy, patients receiving:\n\n     • Clopidogrel (hydrogen sulfate) or Prasugrel (hydrochloride) or Ticlopidine (hydrochloride) without the possibility of discontinuation for 5 days,\n\n     • Low-molecular-weight heparin (LMWH) without the possibility of dose suspension prior to the procedure,\n\n     • Or Fondaparinux without the possibility of discontinuation,\n\n     • Or Abciximab without the possibility of discontinuation for 24 hours and aPTT \\\u003C 50s and ACT \\\u003C 150s,\n\n     • Or Eptifibatide or Tirofiban hydrochloride monohydrate or Argatroban without the possibility of discontinuation 4 hours before the procedure,\n     * Or Bivalirudin without the possibility of discontinuation 2-3 hours before the procedure if CrCL \\> 50 mL\u002Fmin, or 3-5 hours if CrCL \\\u003C 50 mL\u002Fmin,\n     * Or Dabigatran etexilate without the possibility of discontinuation 2-3 days before the procedure if CrCL \\> 50 mL\u002Fmin, or 3-5 days if CrCL \\\u003C 50 mL\u002Fmin.\n   * Vulnerable persons as defined in Articles L1121-5 to L1121-8 :\n\n     • Pregnant women, women in labour, and breastfeeding mothers,\n     * Persons deprived of liberty by judicial or administrative decision, and persons hospitalized without consent under Articles L3212-1 and L3213-1 who do not fall under the provisions of Article L1121-8,\n     * Persons admitted to a health or social care institution for purposes other than research,\n     * Adults under legal protection measures or unable to express their consent.",{"count":321,"type":20},110,[195],"This is a single-center pharmacokinetic study evaluating the impact of residual pembrolizumab levels on the efficacy of salvage chemotherapy following immunotherapy in patients with non-small cell lung cancer (NSCLC) or recurrent and\u002For metastatic head and neck squamous cell carcinoma (HNSCC) not amenable to curative local treatment.",[325,35],"Non-Small Cell Lung Carcinoma (NSCLC)",[327,328,329,330],"Pembrolizumab","immunotherapy","salvage chemotherapy","pharmacokinetics","NOT_YET_RECRUITING","2026-06-04",{"date":211,"type":55},{"date":335,"type":20},"2026-07",{"date":337,"type":20},"2028-12",{"name":339,"class":183},"Centre Antoine Lacassagne",{"id":341,"slug":342,"hasResults":11,"nctId":343,"briefTitle":344,"officialTitle":345,"acronym":346,"eligibilityCriteria":347,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":348,"targetDuration":4,"studyType":21,"phases":350,"briefSummary":351,"conditions":352,"keywords":353,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":368,"lastUpdatePostDateStruct":369,"startDateStruct":371,"completionDateStruct":373,"leadSponsor":375,"locationsCount":378},"100576722","phase-2-fortifi-hn01-a-study-of-ficerafusp-alfa-bca101-or-placebo-in-combination-with-pembrolizumab-in-first-line-pd-l1-pos-r-or-m-hnscc-100576722","NCT06788990","FORTIFI-HN01: A Study of Ficerafusp Alfa (BCA101) or Placebo in Combination With Pembrolizumab in First-Line PD-L1-pos, R or M HNSCC","A Multicenter, Randomized, Double-blind, Phase 2\u002F3 Study of Ficerafusp Alfa (BCA101) or Placebo in Combination With Pembrolizumab for First-Line Treatment of PD-L1-positive, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma","FORTIFI-HN01","Inclusion Criteria:\n\n* Age ≥18 years on the day the Informed Consent Form is signed.\n* Histologically or cytologically confirmed R or M HNSCC. Eligible primary tumor locations are oral cavity, hypopharynx, larynx or oropharynx (with documented HPV-negative disease if presenting with OPSCC). Note: primary tumor location of paranasal sinuses and nasopharynx, any histology are excluded.\n* No prior systemic therapy administered in the R or M setting; and completed systemic therapy \\>6 months prior if given as part of multimodal treatment for locoregionally advanced disease in the adjuvant or definitive setting.\n* Archival tumor tissue or willing to undergo pretreatment biopsy at Screening if archival tissue is insufficient or unavailable.\n* PD-L1 CPS ≥1.\n* Measurable disease based on RECIST 1.1.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n* Adequate organ function, as defined in the protocol.\n\nExclusion Criteria:\n\n* Disease suitable for local therapy administered with curative intent.\n* Prior treatment with anti-TGFβ therapy.\n* Prior therapy with an anti-EGFR antibody (exception: radio sensitizing agents and multimodal treatment for locoregionally advanced disease).\n* Prior history of Grade ≥2 intolerance or hypersensitivity reaction to anti-EGFR therapy or other murine proteins.\n* Prior therapy with an immune checkpoint inhibitor completed within 6 months prior to study treatment initiation.\n* Progressive disease \\\u003C6 months from completion of curative intent systemic therapy for locoregionally advanced HNSCC.\n* Life expectancy less than 3 months.\n* Known active central nervous system metastases, history of spinal cord compression from tumor involvement, a history of carcinomatous meningitis, or leptomeningeal disease are excluded.\n* Current active major bleeding, or a recent major bleeding episode within 4 weeks prior to enrollment.\n* Subject participated in another clinical study or received treatment with another investigational drug must wait at least 5 half-lives of the treatment received or 4 weeks (whichever is shorter) following prior therapy.\n* Active autoimmune disease requiring systemic treatment in the past 2 years.\n* Subjects with chronic hepatitis B virus (HBV) infection with active disease who meet the criteria for anti-HBV therapy and are not on a suppressive antiviral therapy prior to initiation of study treatment.\n* Subjects with a known history of hepatitis C virus (HCV) who have not completed curative antiviral treatment or have an HCV viral load above the limit of quantification at Screening.\n* Known history of human immunodeficiency virus (HIV).\n* Receipt of any organ transplantation, including autologous and allogeneic stem cell transplantation, with the exception of transplants that do not require immunosuppression.\n* Known to be diagnosed and\u002For treated for any other additional malignancy within 2 years prior to randomization with the exception of the following: curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, and curatively resected in situ cervical cancer, and curatively resected in situ breast cancer, and low-risk early stage prostate cancer.\n* Any condition requiring systemic treatment with either corticosteroids (\\>10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 7 days prior to the first dose of study treatment, except for topical, intranasal, intrabronchial, or ocular steroids.\n* Use of a live or live attenuated vaccine within 4 weeks prior to Screening.\n\nOther Inclusion\u002FExclusion criteria may apply as defined in the protocol.",{"count":349,"type":20},650,[23,226],"Ficerafusp alfa is directed against two targets, Epidermal Growth Factor Receptor (EGFR) and Transforming Growth Factor beta (TGF-β).\n\nThis study intends to evaluate the safety and efficacy of ficerafusp alfa in combination with pembrolizumab versus placebo with pembrolizumab in 1L PD-L1-positive, recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC).",[35,206],[354,355,356,357,358,327,359,360,361,362,363,364,365,366,367],"Phase 2\u002F3","Ficerafusp alfa","BCA101","Recurrent Head and Neck Squamous Cell Carcinoma (R HNSCC)","Metastatic Head and Neck Squamous Cell Carcinoma (M HNSCC)","EGFR","TGF-beta","HNSCC","PD-L1+","Head and Neck cancer","Oral Cavity","Oropharynx","Larynx","Hypopharynx","2026-05-29",{"date":370,"type":55},"2026-06-02",{"date":372,"type":55},"2025-01-28",{"date":374,"type":20},"2029-07",{"name":376,"class":377},"Bicara Therapeutics","INDUSTRY",173,{"id":380,"slug":381,"hasResults":11,"nctId":382,"briefTitle":383,"officialTitle":383,"acronym":4,"eligibilityCriteria":384,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":385,"targetDuration":4,"studyType":21,"phases":386,"briefSummary":387,"conditions":388,"keywords":391,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":396,"lastUpdatePostDateStruct":397,"startDateStruct":399,"completionDateStruct":401,"leadSponsor":403,"locationsCount":184},"100609626","phase-1-study-evaluating-18fnota-aby030-for-safety-and-tolerability-of-indeterminate-primary-andor-metastatic-disease-in-head-and-neck-squamous-cell-carcinoma-100609626","NCT07217028","Study Evaluating [18F]NOTA-ABY030 for Safety and Tolerability of Indeterminate Primary and\u002For Metastatic Disease in Head and Neck Squamous Cell Carcinoma","Inclusion Criteria:\n\n1. Age ≥ 18 years.\n2. Subjects diagnosed with any T stage, any subsite within the head and neck. Subjects with recurrent disease or a new primary will be allowed.\n3. Must have evidence of indeterminate metastatic and\u002For primary SCC based on clinical imaging or Primary SCC with suspicious Lymph Nodes standard image modalities prior to surgical removal\n4. Have acceptable lab values, including the following clinical results (if values are considered clinically significant per investigator, participants must be asymptomatic):\n\n   1. Hemoglobin ≥ 9gm\u002FdL\n   2. White blood cell count \\> 3000\u002Fmm3\n   3. Platelet count ≥ 100,000\u002Fmm3\n   4. Serum creatinine ≤ 1.5 times upper reference range\n   5. Potassium\n   6. Magnesium\n   7. Phosphorus\n\nExclusion Criteria:\n\n1. Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina within 6 months prior to enrollment.\n2. Prior severe infusion reactions or hypersensitivity to other monoclonal antibody therapies.\n3. Pregnant (based on Screening serum or urine pregnancy test administered before infusions), or breastfeeding.\n4. Participants with known hypersensitivity to NOTA-ABY-030, cetuximab, murine, or any of the drug components used in this trial.\n5. Subjects with history or evidence of interstitial pneumonitis or pulmonary fibrosis.\n6. Severe renal disease or anuria.\n7. Participants presenting with a baseline QTcF interval \\> than 480 milliseconds.\n8. Those with an allergy to red meat, a history of tick bites, and alpha-gal syndrome will be given extra consideration.",{"count":255,"type":20},[76],"This Phase I, single-institution, open-label study will evaluate the safety, tolerability, and diagnostic performance of \\[18F\\]NOTA-ABY030 PET\u002FCT in patients with head and neck squamous cell carcinoma (HNSCC) who present with indeterminate lesions on standard imaging. The investigational agent is a radiolabeled anti-EGFR affibody designed for rapid clearance and improved tumor-to-background contrast. All participants will receive a 50 mg cetuximab loading dose followed by a bolus of \\[18F\\]NOTA-ABY030, with PET\u002FCT imaging performed at defined intervals to assess biodistribution and lesion uptake. The primary objective is to determine safety and tolerability; secondary objectives include radiation dosimetry and comparison of sensitivity and specificity to conventional imaging modalities (MRI, CT, and \\[18F\\]FDG-PET\u002FCT). This approach aims to improve diagnostic accuracy, reduce unnecessary biopsies, and streamline treatment decisions for patients with HNSCC.",[389,390,260,35],"SCC - Squamous Cell Carcinoma","Radiotracer",[392,393,394,395],"unknown primary","cancer","hnscc","scc","2026-05-06",{"date":398,"type":55},"2026-05-11",{"date":400,"type":55},"2026-04-24",{"date":402,"type":20},"2030-09",{"name":404,"class":183},"Vanderbilt-Ingram Cancer Center",{"id":406,"slug":407,"hasResults":11,"nctId":408,"briefTitle":409,"officialTitle":410,"acronym":4,"eligibilityCriteria":411,"healthyVolunteers":11,"sex":16,"minAge":412,"maxAge":4,"enrollmentInfo":413,"targetDuration":4,"studyType":21,"phases":415,"briefSummary":416,"conditions":417,"keywords":4,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":396,"lastUpdatePostDateStruct":419,"startDateStruct":421,"completionDateStruct":423,"leadSponsor":425,"locationsCount":184},"100496698","phase-1-89zr-panitumumab-with-petct-for-diagnosing-metastases-in-patients-with-head-and-neck-squamous-cell-carcinoma-100496698","NCT05747625","(89Zr Panitumumab) With PET\u002FCT for Diagnosing Metastases in Patients With Head and Neck Squamous Cell Carcinoma","Study Evaluating 89Zr Panitumumab for Assessment of Indeterminate Metastatic Lesions on 18F-FDG-PET\u002FCT in Head and Neck Squamous Cell Carcinoma","Inclusion Criteria:\n\n* Age \\>= 19 years\n* Biopsy confirmed diagnosis of squamous cell carcinoma of the head and neck\n* Subjects diagnosed with any T stage, any subsite within the head and neck. Subjects with recurrent disease or a new primary will be allowed\n* Must have evidence of indeterminate metastatic squamous cell carcinoma (SCC) based on 18F-fluorodeoxyglucose (FDG)-PET\u002FCT or Primary SCC with suspicious Lymph Nodes on CT prior to surgical removal\n* Hemoglobin \\>= 9gm\u002FdL\n* White blood cell count \\> 3000\u002Fmm\\^3\n* Platelet count \\>= 100,000\u002Fmm\\^3\n* Serum creatinine =\\\u003C 1.5 times upper reference range\n\nExclusion Criteria:\n\n* Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina within 6 months prior to enrollment\n* History of infusion reactions to other monoclonal antibody therapies\n* Pregnant (based on screening serum pregnancy test and day 0 urine pregnancy test administered before unlabeled panitumumab), or breastfeeding\n* Magnesium or potassium lower than the normal institutional values\n* Subjects receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents\n* Subjects with a history or evidence of interstitial pneumonitis or pulmonary fibrosis\n* Severe renal disease or anuria\n* Known hypersensitivity to deferoxamine or any of its components","19 Years",{"count":414,"type":20},60,[76],"The goal of this phase I clinical trial is to evaluate the usefulness of an imaging test (zirconium Zr89 panitumumab \\[89Zr panitumumab\\]) with positron emission tomography (PET)\u002Fcomputed tomography (CT) for diagnosing the spread of disease from where it first started (primary site) to other places in the body (metastasis) in patients with head and neck squamous cell carcinoma. Traditional PET\u002FCT has a low positive predictive value for diagnosing metastatic disease in head and neck cancer. 89Zr panitumumab is an investigational imaging agent that contains radiolabeled anti-EGFR antibody which is overexpressed in head and neck cancer. The main question this study aims to answer is the sensitivity and specificity of 89Zr panitumumab for the detection of indeterminate metastatic lesions in head and neck cancer.\n\nParticipants will receive 89Zr panitumumab infusion and undergo 89Zr panitumumab PET\u002FCT 1 to 5 days after infusion. Participants will otherwise receive standard of care evaluation and treatment for their indeterminate lesions.\n\nResearchers will compare the 89Zr panitumumab to standard of care imaging modalities (magnetic resonance imaging (MRI), CT, and\u002For PET\u002FCT).",[260,35,418],"Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck",{"date":420,"type":55},"2026-05-08",{"date":422,"type":55},"2023-05-09",{"date":424,"type":20},"2030-03-01",{"name":426,"class":183},"Eben Rosenthal",{"id":428,"slug":429,"hasResults":11,"nctId":430,"briefTitle":431,"officialTitle":432,"acronym":4,"eligibilityCriteria":433,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":434,"targetDuration":4,"studyType":21,"phases":435,"briefSummary":436,"conditions":437,"keywords":4,"overallStatus":331,"whyStopped":4,"lastUpdateSubmitDate":453,"lastUpdatePostDateStruct":454,"startDateStruct":455,"completionDateStruct":457,"leadSponsor":459,"locationsCount":184},"100638080","phase-2-low-dose-reduced-frequency-nivolumab-for-the-treatment-of-unresectable-or-metastatic-cancer-afford-io-trial-100638080","NCT07576725","Low Dose, Reduced Frequency Nivolumab for the Treatment of Unresectable or Metastatic Cancer, AFFORD IO Trial","AFFORD IO: A Phase 2 Trial of Low Dose, Reduced Frequency Nivolumab (Anti-PD-1 Antibody) in Patients With Unresectable or Metastatic Cancer","Inclusion Criteria:\n\n* Participants are eligible if they have one of these histologically confirmed, unresectable or metastatic cancer types listed below, based upon historical responsiveness to anti-PD-(L)1 agents\n\n  * Non-small cell lung cancer (NSCLC) with documented PD-L1 expression (combined positive score \\[CPS\\] ≥ 1) (NOTE: Participants with known driver oncogenic mutations\u002Frearrangements, including EGFR, ALK and ROS-1, will be excluded.)\n  * Head and neck squamous cell carcinoma (HNSCC) with documented PD-L1 expression (CPS ≥ 1)\n  * Clear cell renal cell carcinoma (ccRCC) (NOTE: Other subtypes may be permitted after approval by the Medical Monitor)\n  * Melanoma (cutaneous, acral-lentiginous and mucosal subtypes), and non-melanoma skin cancers, (cutaneous squamous cell carcinoma \\[CSCC\\], basal cell carcinoma \\[BCC\\] and Merkel cell carcinoma \\[MCC\\])\n  * Hodgkin's lymphoma\n  * Urothelial carcinoma\n  * Cervical cancer with documented PD-L1 expression (CPS ≥ 1)\n  * Colorectal cancer with high microsatellite instability (MSI) or mismatch repair deficiency\n  * Kaposi sarcoma (KS) without clinical concern for multicentric Castleman's disease (MCD)\n  * Any cancer type with historical data suggesting an ORR \\> 20% with anti-PD(L)-1 agents (NOTE: All participants in this category must be approved by the Medical Monitor prior to enrollment.)\n* Must have experienced disease progression after or deemed not to be a good candidate for available curative systemic therapy options\n* Presence of at least one measurable tumor, per RECIST v1.1\n* Age 18 or older. (NOTE: Both men and women, and members of all races and ethnic groups are eligible for this trial.)\n* Eastern Cooperative Oncology Group (ECOG) performance score of 0-2\n* Absolute neutrophil count (ANC) ≥ 1.0 × 10\\^9\u002FL\n* Platelet count ≥ 75 × 10\\^9\u002FL\n* Hemoglobin ≥ 9 g\u002FdL (NOTE: Participants may have been transfused)\n* Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) (or total bilirubin ≤ 2.5 × upper limit of normal \\[ULN\\] in participants with Gilbert's syndrome)\n* Estimated creatinine clearance ≥ 30mL\u002Fmin according to the Cockcroft-Gault formula or according to local institutional standard\n* Must consent to undergo serial research blood draws at study defined timepoints, unless deemed unsafe or not feasible by the treating investigator\n* Must have an ability to understand and provide consent to the institutional review board (IRB)-approved informed consent form (ICF) document(s)\n* Women of childbearing potential must have a negative serum or urine pregnancy test at screening\n* Both male and female participants must be willing to use highly effective contraception, as stipulated in national or local guidelines, throughout the study and for at least 180 days after the last treatment administration, if the risk of conception exists\n\nExclusion Criteria:\n\n* Prior exposure to any immune-checkpoint inhibitor for any reason\n* Residual adverse event(s) from prior therapy grade \\> 1 (National Cancer Institute \\[NCI\\]-Common Terminology Criteria for Adverse Events \\[CTCAE\\] v6.0) that could interfere with study endpoints or put participant safety at risk, as determined by the treating investigator\n* Known active central nervous system (CNS) metastases and\u002For prior history of leptomeningeal cancer involvement\n* Known history of another active malignancy (besides the eligible cancer diagnosis) within the last 3 years from day 1 of nivolumab that could interfere with study endpoints or put participant safety at risk. (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ \\[skin, bladder, cervical, colorectal, breast\\] or low grade prostatic intraepithelial neoplasia or grade 1 prostate cancer. Any other neoplasm, which has been treated adequately and is adjudged by the treating investigator to have a low risk of progression during the study, could be enrolled only after approval from the medical monitor.)\n* Known active hepatitis B virus (HBV) or hepatitis C virus (HCV), defined as follows:\n\n  * Active HBV is defined as a known positive hepatitis B virus surface antigen (HBsAg) result or positive total hepatitis B virus core antibody (anti-HBc) results in the absence of hepatitis B virus surface antibody (anti-HBsAb). (NOTE: When HBsAg is negative and HBcAb is positive, HBV-DNA should be measured. When HBV-deoxyribonucleic acid \\[DNA\\] is negative, this participant could be enrolled with close monitoring of HBV activities.)\n  * Active hepatitis C virus (HCV) is defined as a known positive HCV antibody result and quantitative HCV-ribonucleic acid (RNA) results greater than the lower limits of detection of the assay. (NOTE: Participants who have had definitive treatment for HCV are permitted if HCV-RNA is undetectable.)\n* Known uncontrolled HIV infection. (NOTE: HIV-infected participants may be allowed if all the following criteria are met: CD4 count ≥ 100\u002FμL, viral load less than 200 copies\u002FmL, and clinically stable on antiretroviral therapy \\[ART\\] for at least 3 months.)\n\n  * These participants will be enrolled only after approval from the medical monitor\n* Known active autoimmune disease or an allograft requiring systemic immunosuppression with corticosteroids (\\> 10 mg\u002Fday of prednisone or equivalent) or immunosuppressive drugs within the past 2 years before the first dose of nivolumab. (NOTE: Exceptions will be made for participants with autoimmune conditions such as diabetes type I, vitiligo, psoriasis, hypothyroid or hyperthyroid diseases not requiring immunosuppressive treatment; participants receiving physiologic corticosteroid replacement therapy at doses \\\u003C 10 mg\u002Fday of prednisone or equivalent for adrenal or pituitary insufficiency; participants with a condition such as asthma or chronic obstructive pulmonary disease that requires intermittent use of steroids or those who require brief courses of corticosteroids for prophylaxis \\[e.g., contrast dye allergy\\], nivolumab-related standard premedication, and\u002For treatment of non-serious immune related adverse events. Any other situation must be discussed with the medical monitor for risk\u002Fbenefit assessment.)\n* Immunosuppressed status due to severe uncontrolled diabetes, concurrent uncontrolled hematological malignancy, or other comorbidities\n* Known history of serious, active infections (aside from well-controlled HIV, as per exclusion criterion #6) requiring systemic antimicrobial agents within 14 days before the first dose of nivolumab. (NOTE: Chronic infections such as herpes simplex virus requiring suppressive therapy may be allowed after discussion with the medical monitor for risk\u002Fbenefit assessment.)\n* Known history of clinically significant interstitial lung disease, or active noninfectious pneumonitis\n* Clinically significant (i.e., active) cardiovascular disease such as cerebral vascular accident or myocardial infarction within 6 months prior to first dose of nivolumab, ongoing unstable angina or congestive heart failure (New York Heart Association Classification class II-IV), or serious cardiac arrhythmia that could jeopardize participant safety on the study\n* Receipt of live vaccine(s) within 30 days of planned start of nivolumab. (NOTE: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster \\[chickenpox\\], yellow fever, rabies, bacillus Calmette Guerin \\[BCG\\], and typhoid vaccines. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed.)\n* Known severe acute or chronic medical conditions such as uncontrolled seizure disorder, serious psychiatric illness, or laboratory abnormalities, that may increase the risk associated with study participation or may interfere with the interpretation of study endpoints and, in the judgment of the treating investigator, would make the participant inappropriate for entry into this study\n* Known active tuberculosis (TB). (NOTE: Participants with latent TB will be allowed, provided they are receiving tuberculosis preventive therapy, after approval of the medical monitor.)\n* Known allergy or hypersensitivity to any component of the study drug formulation (including excipients and additives) that could interfere with study endpoints or put participant safety at risk\n* Pregnant or breast-feeding woman",{"count":281,"type":20},[23],"This phase II trial studies how well low dose, reduced frequency nivolumab works in treating patients with cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Nivolumab is a type of immune checkpoint inhibitor (ICI). ICIs have revolutionized the treatment of numerous cancers with remarkable improvement in participant outcomes. However, accessibility of ICIs is extremely poor on a global scale, mainly due to high costs. Previous research has suggested that these drugs can be given at lower doses and reduced frequency than their approved dosing regimens, with similar results. Giving nivolumab at a lower dose and less often may help reduce the cost of therapy, improve immunotherapy accessibility, and therefore improve survival outcomes globally.",[26,438,28,439,440,441,442,443,113,444,296,297,35,445,118,119,120,446,122,124,126,447,172,128,129,142,301,173,145,146,448,449,156,450,451,302,160,162,163,164,452,166,168],"Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8","Hodgkin Lymphoma","Kaposi Sarcoma","Metastatic Acral Lentiginous Melanoma","Metastatic Basal Cell Carcinoma","Metastatic Clear Cell Renal Cell Carcinoma","Metastatic Kaposi Sarcoma","Metastatic Mucosal Melanoma","Stage III Colorectal Cancer AJCC v8","Unresectable Acral Lentiginous Melanoma","Unresectable Basal Cell Carcinoma","Unresectable Clear Cell Renal Cell Carcinoma","Unresectable Colorectal Carcinoma","Unresectable Mucosal Melanoma","2026-05-01",{"date":420,"type":55},{"date":456,"type":20},"2026-09-01",{"date":458,"type":20},"2029-08-31",{"name":460,"class":183},"Fred Hutchinson Cancer Center",{"id":462,"slug":463,"hasResults":11,"nctId":464,"briefTitle":465,"officialTitle":466,"acronym":4,"eligibilityCriteria":467,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":468,"targetDuration":4,"studyType":21,"phases":470,"briefSummary":472,"conditions":473,"keywords":4,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":490,"lastUpdatePostDateStruct":491,"startDateStruct":493,"completionDateStruct":495,"leadSponsor":497,"locationsCount":184},"100566967","remote-audiometry-to-monitor-for-treatment-related-hearing-loss-in-patients-with-hn-scc-receiving-cisplatin-andor-radiation-100566967","NCT06662058","Remote Audiometry to Monitor for Treatment-Related Hearing Loss in Patients With H&N SCC Receiving Cisplatin and\u002For Radiation","Ototoxicity Monitoring and Remote Audiometry","Inclusion Criteria:\n\n* Adult patients, male or female, aged ≥ 18, able to provide informed consent\n* Subjects with pathologically proven HNSCC involving the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, skin, or paranasal sinuses; patients with unknown primary HNSCC involving the cervical lymph nodes can also be included. Patients can have previously untreated or recurrent\u002Fmetastatic disease\n* Subjects who will be treated with cisplatin chemotherapy and\u002For radiation. For radiation alone, patients should have tumors near the inner ear, including the nasopharynx, temporal bone, and\u002For parotid salivary gland\n* Life expectancy of more than 3 months, as determined by the investigator\n\nExclusion Criteria:\n\n* Patients with profound hearing loss in both ears, which precludes an accurate hearing test. This can be determined based on patient report\u002Fhistory or audiogram done before or after informed consent\n* Patients who are unable to participate in a hearing test (per the investigator's judgment)",{"count":469,"type":20},118,[471],"NA","This clinical trial tests the impact of offering hearing tests (audiometry) close to home and remotely on participation in monitoring for treatment-related hearing loss in patients with head and neck squamous cell cancer receiving cisplatin and\u002For radiation. Cisplatin, a chemotherapy often used to treat head and neck cancers, and radiation given near the ear can cause hearing loss in some patients. Hearing loss can have a major negative impact on quality of life, contributing to social isolation and frustration. Identifying hearing changes may allow treatment changes to prevent further loss. Audiometry measures hearing loss using a graphic record of the softest sounds that a person can hear at various frequencies. It is recommended patients have a hearing test before, during and after treatment to monitor for any hearing loss. This is usually done in the office and performed on the same day as other visits whenever possible, however, patients who live far away or have stage IV cancer, may have more difficulty coming back for hearing tests. Offering close to home and remote audiometry may improve monitoring for hearing loss in patients with head and neck squamous cell cancer receiving cisplatin and\u002For radiation.",[29,474,475,260,476,477,478,35,36,37,479,39,40,480,481,482,483,484,485,206,229,230,486,232,233,487,143,46,47,48,488,49,489],"Cutaneous Squamous Cell Carcinoma of the Head and Neck","Head and Neck Carcinoma of Unknown Primary","Hypopharyngeal Squamous Cell Carcinoma","Laryngeal Squamous Cell Carcinoma","Metastatic Cutaneous Squamous Cell Carcinoma of the Head and Neck","Metastatic Nasopharyngeal Squamous Cell Carcinoma","Metastatic Paranasal Sinus Squamous Cell Carcinoma","Nasopharyngeal Squamous Cell Carcinoma","Oral Cavity Squamous Cell Carcinoma","Oropharyngeal Squamous Cell Carcinoma","Paranasal Sinus Squamous Cell Carcinoma","Recurrent Cutaneous Squamous Cell Carcinoma of the Head and Neck","Recurrent Nasopharyngeal Squamous Cell Carcinoma","Recurrent Paranasal Sinus Squamous Cell Carcinoma","Stage IV Nasopharyngeal Carcinoma AJCC v8","Stage IV Sinonasal Cancer AJCC v8","2026-04-20",{"date":492,"type":55},"2026-04-23",{"date":494,"type":55},"2025-03-12",{"date":496,"type":20},"2029-10-31",{"name":498,"class":183},"Emory University",{"id":500,"slug":501,"hasResults":11,"nctId":502,"briefTitle":503,"officialTitle":504,"acronym":505,"eligibilityCriteria":506,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":507,"targetDuration":4,"studyType":21,"phases":509,"briefSummary":510,"conditions":511,"keywords":512,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":518,"lastUpdatePostDateStruct":519,"startDateStruct":521,"completionDateStruct":523,"leadSponsor":525,"locationsCount":527},"100521075","phase-3-a-study-of-ficlatuzumab-in-combination-with-cetuximab-in-participants-with-recurrent-or-metastatic-rm-hpv-negative-head-and-neck-squamous-cell-carcinoma-100521075","NCT06064877","A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R\u002FM) HPV Negative Head and Neck Squamous Cell Carcinoma","A Multicenter, Randomized, Double Blind, Placebo - Controlled, Phase 3 Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R\u002FM) HPV -Negative Head and Neck Squamous Cell Carcinoma. (FIERCE-HN)","FIERCE-HN","Inclusion Criteria:\n\n* Male or female and ≥ 18 years of age\n* Histologically and\u002For cytologically confirmed primary diagnosis of R\u002FM HNSCC\n* Participants with oropharyngeal cancer will be required to have proof of p16 negative status submitted on the basis of a pathology report\n* At least 1 measurable lesion by contrast CT or MRI scan according to RECIST v.1.1. Such lesions must not have been previously irradiated; if the measurable lesion(s) has been irradiated, clear progression must be documented\n* Participants must have failed prior therapy with an anti-PD-1\u002FPD-L1 ICI and with platinum-based chemotherapy administered in combination or sequentially, in either the locally advanced or R\u002FM setting. Failure of prior treatment may be due to progression of disease or intolerance to treatment\n* Patient's tumor must be considered inoperable and incurable\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with a life expectancy of at least 12 weeks\n* For women of childbearing potential (WOCBP), documentation of negative serum pregnancy test within 30 days of randomization\n* For WOCBP and male participants whose sexual partners are of childbearing potential, agreement to use an effective method of contraception during the study and for at least 5 months after the last dose of study treatment. Birth control methods which may be considered highly effective include methods that achieve a failure rate of less than 1% per year when used consistently and correctly.\n* Ability to give written informed consent and comply with protocol requirements\n* Patients with feeding tubes are eligible for the study.\n* Archived tissue sample must be submitted to the Sponsor-designated laboratory within 60 days of randomization for c-Met analysis (if a tissue sample is not available, a fresh biopsy may be required prior to enrollment)\n\nExclusion Criteria:\n\n* Participants who have received \\> 2 prior lines of anticancer therapy or prior treatment with cetuximab\u002Falternative EGFR inhibitors for the treatment of R\u002FM HNSCC\n* History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent or cetuximab\n* Known or suspected untreated and uncontrolled brain metastases or leptomeningeal carcinomatosis Note: Participants with locally treated brain metastases are eligible provided 2 weeks have elapsed since local therapy. Participants are allowed to continue steroid taper during the start of study treatment.\n* Prior treatment with any other investigational drug or biologic agent or radiation therapy before a washout has been completed (must be completed prior to randomization):\n\n  1. 2 weeks (14 days) or 5 half-lives, whichever is shorter, for chemotherapeutic agents, small molecules, and checkpoint inhibitors\n  2. 3 weeks (21 days) or 5 half-lives, whichever is shorter, for antibody-drug conjugates\n  3. 4 weeks (28 days) for cell therapies\n  4. 2 weeks (14 days) for radiation therapy\n* Any unresolved and significant toxicity (National Cancer Institute Common Terminology Criteria for Adverse Events \\[NCI-CTCAE\\] version 5.0) Grade 2 or greater from previous anticancer therapy (including radiation therapy), other than alopecia\n* Significant cardiovascular disease, including: Cardiac failure New York Heart Association class III or IV; Myocardial infarction, severe or unstable angina within 6 months prior to randomization; History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)\n* Any other medical condition or psychiatric condition that, in the opinion of the Investigator, might interfere with the participant's involvement in the study or interfere with the interpretation of study results\n* History of prior malignancy within 2 years prior to randomization (except for adequately treated non-melanoma skin cancer, carcinoma in situ of the breast or cervix, superficial bladder cancer, or early-stage prostate cancer, without evidence of recurrence; participants may or may not be on maintenance therapy)\n* Participants who are positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) with indication of acute or chronic hepatitis (as defined in protocol)\n* Radiographic evidence (historical or at screening) of interstitial lung disease or idiopathic pulmonary fibrosis\n* Female participants who are pregnant or breastfeeding\n\nA full list of inclusion and exclusion criteria can be found in the protocol.",{"count":508,"type":20},410,[226],"The purpose of this study is to compare the efficacy and safety of ficlatuzumab plus cetuximab compared to placebo plus cetuximab in participants with recurrent\u002Fmetastatic (R\u002FM) HPV-negative Head and Neck Cancer.\n\nThe primary hypothesis is that ficlatuzumab combined with cetuximab is superior to cetuximab alone in terms of progression-free survival and\u002For overall survival.",[263,206],[513,514,515,516,517],"Recurrent","Metastatic","HPV-negative","Head and Neck","Squamous Cell Carcinoma","2026-04-06",{"date":520,"type":55},"2026-04-09",{"date":522,"type":55},"2024-01-11",{"date":524,"type":20},"2027-11",{"name":526,"class":377},"AVEO Pharmaceuticals, Inc.",112,{"id":529,"slug":530,"hasResults":11,"nctId":531,"briefTitle":532,"officialTitle":533,"acronym":4,"eligibilityCriteria":534,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":535,"targetDuration":4,"studyType":21,"phases":537,"briefSummary":538,"conditions":539,"keywords":541,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":551,"lastUpdatePostDateStruct":552,"startDateStruct":553,"completionDateStruct":555,"leadSponsor":557,"locationsCount":559},"100442877","alpha-radiation-emitters-device-dart-in-combination-with-check-point-inhibitor-for-the-treatment-of-recurrent-unresectable-or-mhnscc-100442877","NCT05047094","Alpha Radiation Emitters Device (DaRT) in Combination With Check Point Inhibitor for the Treatment of Recurrent Unresectable or mHNSCC","A Safety and Efficacy Study of Intratumoral Diffusing Alpha Radiation Emitters in Recurrent Unresectable or Metastatic Head and Neck Squamous Cell Carcinoma","Inclusion Criteria:\n\n1. Pathologically confirmed, metastatic, or recurrent unresectable squamous cell carcinoma of the head and neck.\n2. Ability to provide tissue sample, either from an archive or undergo another biopsy to provide a fresh sample\n3. Targetable lesion must be technically amenable for the DaRT seeds implantation\n4. Brachytherapy indication validated by a multidisciplinary team\n5. Targetable lesion according to RECIST v1.1\n6. Age ≥ 18 years old\n7. Eastern Cooperative Oncology Group (ECOG) Performance Status Scale ≤ 2\n8. Subjects' life expectancy is more than 6 months\n9. White Blood Count (WBC) ≥ 3500\u002Fµl, granulocyte ≥ 1500\u002Fµl\n10. Platelet count ≥ 100,000\u002Fµl\n11. Hemoglobin ≥ 9 g\u002Fdl\n12. Calculated or measured creatinine clearance ≥ 60 cc\u002Fmin\n13. Aspartate Aminotransferase (AST) and Alanine Transaminase (ALT) ≤ 2.5 X Upper Limit of Normal (ULN) or ≤ 5 X ULN for subjects with liver metastases\n14. International normalized ratio (INR) \\\u003C1.4 for patients not on Warfarin\n15. Subjects are willing and able to sign an informed consent form\n16. Women of childbearing potential (WOCBP) will have evidence of negative pregnancy test before the Ra-224 implantation and are required to use an acceptable contraceptive method to prevent pregnancy for 3 months after brachytherapy.\n\nExclusion Criteria:\n\n1. Previous treatment for metastatic disease (for recurrent unresectable disease, previous treatment is allowed given that 6 months had elapsed from completion of treatment for primary disease)\n2. Patients with brain metastases\n3. Combined Positive Scores (CPS) \\\u003C1\n4. Patients with known contraindications to radiotherapy\n5. Any prior therapy with anti-PD-L1 (Programmed death-ligand), anti-PD-L2, anti-CTLA-4 (Cytotoxic T lymphocyte antigen) antibody, etc.\n6. Any history of a sever hypersensitivity reaction to any monoclonal antibody.\n7. Known hypersensitivity to any of the components of the DaRT.\n8. Has a known history of active TB (Tuberculosis Bacillus )\n9. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.\n10. Any diagnosis of immunodeficiency or current immunosuppressive therapy including \\>10mg\u002Fday of prednisone within 14 days of enrollment is not permitted\n11. Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 12 months.\n12. Patients with uncontrolled intercurrent illnesses including, but not limited to an active infection requiring systemic therapy or a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial or interfere with the study endpoints.\n13. Patient requires treatment which may conflict with the endpoints of this study including evaluation of response or toxicity of DaRT.\n14. Has a known history of Human immunodeficiency virus (HIV) (HIV 1\u002F2 antibodies).\n15. Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA \\[qualitative\\] is detected)\n16. Pregnancy or lactation.\n17. Patients must agree to use adequate contraception (abstinence, barrier method of birth control, or any other medically acceptable form of contraception) prior to study entry, for the duration of study participation and for 6 months after last dose of Pembrolizumab.",{"count":536,"type":20},48,[471],"A unique combinational treatment for cancer employing intratumoral diffusing alpha radiation emitter device with check point inhibitor for recurrent unresectable or metastatic Head and Neck Squamous Cell Carcinoma",[260,540,263],"Skin Cancer",[517,542,540,543,361,544,545,546,547,327,548,549,550],"SCC","Skin metastasis","Carcinoma, Squamous","Recurrent disease","Alpha radiation","Brachytherapy","Check Point Inhibitor","KEYTRUDA","Immunomodulators","2026-03-31",{"date":518,"type":55},{"date":554,"type":55},"2021-11-02",{"date":556,"type":20},"2027-06",{"name":558,"class":377},"Alpha Tau Medical LTD.",3,{"id":561,"slug":562,"hasResults":11,"nctId":563,"briefTitle":564,"officialTitle":565,"acronym":4,"eligibilityCriteria":566,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":567,"targetDuration":4,"studyType":21,"phases":569,"briefSummary":570,"conditions":571,"keywords":4,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":572,"lastUpdatePostDateStruct":573,"startDateStruct":575,"completionDateStruct":577,"leadSponsor":579,"locationsCount":184},"100391315","phase-2-cetuximab-after-immunotherapy-for-the-treatment-of-head-and-neck-squamous-cell-cancer-100391315","NCT04375384","Cetuximab After Immunotherapy for the Treatment of Head and Neck Squamous Cell Cancer","Pilot Phase II Study to Evaluate Effect of Cetuximab Given as Single Agent After Immunotherapy With PD-1 Inhibitors in Patients With Head and Neck Squamous Cell Carcinoma","Inclusion Criteria:\n\n* Patients must have histologically or cytologically confirmed head and neck squamous cell carcinoma.\n* Measurable disease by scans- at least one measurable lesion.\n* Patients must have received previous treatment with immunotherapy with PD-1 inhibitor alone or in combination with chemotherapy.\n* Patients must have a Performance Status of 0-2.\n* Patients must be greater than or equal to 18 years old.\n* Participant is willing and able to comply with the protocol for the duration of the study.\n* Ability to understand and the willingness to sign an Institutional Review Board-approved informed consent document.\n\nExclusion Criteria:\n\n* Prior treatment with Cetuximab or prior therapy that specifically and directly targets the epidermal growth factor receptor (EGFR) pathway in the last five (5) years.\n* Prior allergic reaction to Cetuximab.\n* History of allergic reactions attributed to compounds of chemical or biologic composition similar to those of Cetuximab.\n* Patients receiving any other investigational agents.\n* Patient is on medications that need to be continued and that might interact with Cetuximab.\n* Any uncontrolled condition, which in the opinion of the investigator, would interfere in the safe and timely completion of study treatment and procedures.\n* Participant with a history of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on screening chest imaging.\n\nAny of the following conditions:\n\n* Serious or non-healing wound, ulcer, or bone fracture at the discretion of treating physician\n* history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study enrollment\n* history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study enrollment\n* history of myocardial infarction, ventricular arrhythmia, stable\u002Funstable angina, -symptomatic congestive heart failure, coronary\u002Fperipheral artery bypass graft or stenting or other significant cardiac disease within 6 months prior to study enrollment\n* history of arterial or venous thrombosis\u002Fthromboembolic event, including pulmonary embolism within 6 months of study enrollment\n* any condition requiring the use of immunosuppression, excluding rheumatologic conditions treated with stable doses of corticosteroids.\n\nPregnancy, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment.",{"count":568,"type":20},38,[23],"This is a Phase II treatment, non-randomized, open label clinical trial to study the efficacy of the Cetuximab when administered as single agent in recurrent\u002F metastatic head and neck squamous cell carcinoma after the failure or intolerance of immuno-oncology or immuno-oncology combined with chemotherapy.",[260,206,263],"2026-03-17",{"date":574,"type":55},"2026-03-18",{"date":576,"type":55},"2020-07-01",{"date":578,"type":20},"2027-12",{"name":580,"class":183},"Wake Forest University Health Sciences",{"id":582,"slug":583,"hasResults":11,"nctId":584,"briefTitle":585,"officialTitle":586,"acronym":4,"eligibilityCriteria":587,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":588,"targetDuration":4,"studyType":21,"phases":590,"briefSummary":591,"conditions":592,"keywords":4,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":593,"lastUpdatePostDateStruct":594,"startDateStruct":596,"completionDateStruct":598,"leadSponsor":599,"locationsCount":272},"100532325","phase-1-losartan-pembrolizumab-and-stereotactic-body-radiation-therapy-for-the-treatment-of-patients-with-locally-recurrent-refractory-or-oligometastatic-head-and-neck-squamous-cell-carcinoma-100532325","NCT06211335","Losartan, Pembrolizumab and Stereotactic Body Radiation Therapy for the Treatment of Patients With Locally Recurrent, Refractory or Oligometastatic Head and Neck Squamous Cell Carcinoma","Phase Ib Study of Losartan, Pembrolizumab and Stereotactic Body Radiation Therapy (SBRT) in Patients With Locoregionally Recurrent, Refractory, or Oligometastatic Head and Neck Squamous Cell Carcinoma (HNSCC)","Inclusion Criteria:\n\n* Histologically or cytologically confirmed locoregionally recurrent, refractory, or oligometastatic (at most 4 lesions) squamous cell carcinoma of the head and neck not amenable to curative resection\n* p16 status known for base of tongue, soft palate, and tonsil cancers\n* Tumor amenable to sequential biopsies, and patients willing to undergo sequential tumor biopsies so long as the treating investigator considers them to be clinically safe\n* Prior radiotherapy to the head and neck is allowed. Disease should be limited to up to 4 sites of active disease in the head and neck and\u002For distant metastatic sites if deemed safely treatable by physician, or adjacent sites treatable in single contiguous target volume with a recommended maximum total tumor dimension (GTV) of \\\u003C 7.5 cm. However, larger volumes may be allowed after discussion with primary investigator (PI) and careful review of radiation dose constraints\n* Prior systemic therapy is allowed. Patients with locoregional relapses where radiation alone would be indicated are allowed to enroll without prior systemic therapy\n* Presence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) with a target on a computed tomography (CT) scan or magnetic resonance imaging (MRI) available for review\n* Combined positive score (CPS) \\> 1%\n* Age ≥ 18 years at time of consent\n* Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1\n* Leukocytes ≥ 3 × 10\\^9\u002FL\n* Absolute neutrophil count ≥ 1.5 × 10\\^9\u002FL\n* Platelets ≥ 100 × 10\\^9\u002FL\n* Hemoglobin (Hgb) ≥ 9 g\u002FdL, transfusions may be used to raise Hgb to ≥ 9 g\u002FdL (no washout required)\n* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)\n* Aspartate transaminase (AST) \u002F alanine transaminase (ALT) ≤ 2.5 × institutional ULN\n* Creatinine within normal institutional limits OR creatinine clearance ≥ 30 mL\u002Fmin\u002F1.73 m\\^2 for patients with creatinine above institutional ULN\n* The effects of losartan on the developing human fetus are unknown. For this reason, individuals of childbearing potential and male participants with partners of childbearing potential, must agree to use methods of contraception for the duration of study participation (including dosing interruptions) and for up to 3 months after last study treatment; or be surgically sterilized\n* Ability to understand and willingness to sign and date the informed consent form\n* Stated ability and willingness to adhere to the study visit schedule and protocol requirements\n\nExclusion Criteria:\n\n* Nasopharyngeal carcinoma, salivary gland carcinoma or primary skin squamous cell carcinoma (SCC)\n* Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody\n* Chemotherapy or other anti-cancer therapy within 3 weeks prior to study day 1\n* Hypersensitivity to losartan or any component of the formulation\n* Radiation therapy within 6 months prior to study day 1\n* Patients with disease surrounding \\> 50% of the carotid\n* Participant who has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade ≤ 1 from an adverse event (AE) due to previous cancer therapeutics (i.e., chemotherapy, radiation therapy, biologic therapy, and\u002For experimental therapy) with the exception of alopecia\n* Major surgery as assessed by the investigator (with the exception of diagnostic biopsy) within ≤ 28 days prior to study day 1 (patients must have completely recovered from any previous surgery prior to study day 1)\n* Clinically significant bleeding ≤ 4 weeks prior to study day 1\n* Requirement for parenteral antibiotics, or any active infection requiring parenteral antibiotic therapy within 4 weeks prior to study day 1\n* Clinically significant or uncontrolled diabetes mellitus (hemoglobin A1C ≤ 8.5%). Patients with diabetes mellitus treated with aliskiren ≤ 7 days prior to study day 1 are excluded\n* Active autoimmune disorders that have required systemic treatment with disease modifying agents, corticosteroids, or immunosuppressive drugs in the past 2 years are excluded. Patients with autoimmune disorder or well-managed or inactive autoimmune disorders, such as Hashimoto's thyroiditis, may be allowed at the discretion of the PI\n* Current use of systemic corticosteroids equivalent to \\>10 mg of prednisone per day\n* Current use of angiotensin receptor blockers (ARBs) or angiotensin converting enzyme (ACE) inhibitors for management of hypertension\n* Clinically significant cardiovascular, pulmonary, endocrine, neurologic, gastrointestinal or genitourinary disease unrelated to underlying solid tumor that in the judgment of the investigator should preclude treatment with losartan\n* Any other active malignancy except for low-risk prostate cancer previously treated or under active surveillance, uncomplicated and cured basal cell carcinoma, or squamous cell carcinoma of the skin within 5 years of study entry\n* Known history of positive hepatitis C (HCV) antibody, hepatitis B (HBV) surface antigen (HbsAg and HBV core Ab positive), or human immunodeficiency virus (HIV) antibody results. Patients with positive antibody tests are eligible with negative viral loads\n* Administration of live, attenuated vaccine ≤ 28 days prior to study day 1. Administration of inactivated flu vaccines is allowed\n* Any prior treatment with losartan or other specific TGF-β-directed therapy\n* Treatment with another investigational drug or device, or approved therapy for investigational use ≤ 28 days prior to study day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to study day 1, whichever may be longer\n* Pregnant or breast feeding\n* Any condition that in the opinion of the investigator would interfere with the participant's safety, compliance while on trial, or understanding or rendering of informed consent",{"count":589,"type":20},24,[76],"This phase Ib trial tests the safety, side effects and how well losartan, pembrolizumab and stereotactic body radiation therapy (SBRT) for the treatment of patients with head and neck squamous cell carcinoma that has come back to nearby tissue or lymph node after a period of improvement (locally recurrent), that has not responded to previous treatment (refractory) or that has spread from where it first started to multiple other placed in the body (oligometastatic). Losartan is a drug used to treat high blood pressure that may enhance the effects of other cancer treatments such as immunotherapy and radiation. Immunotherapy with pembrolizumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Giving losartan, pembrolizumab and SBRT may work better in treating patients with locally recurrent, refractory or oligometastatic head and neck squamous cell carcinoma.",[30,35,234],"2026-03-10",{"date":595,"type":55},"2026-03-12",{"date":597,"type":55},"2023-12-07",{"date":556,"type":20},{"name":600,"class":183},"University of California, Davis",{"id":602,"slug":603,"hasResults":11,"nctId":604,"briefTitle":605,"officialTitle":606,"acronym":4,"eligibilityCriteria":607,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":608,"targetDuration":4,"studyType":21,"phases":610,"briefSummary":611,"conditions":612,"keywords":616,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":618,"lastUpdatePostDateStruct":619,"startDateStruct":621,"completionDateStruct":623,"leadSponsor":624,"locationsCount":272},"100582832","phase-1-tmv-vaccine-therapy-alone-and-with-pembrolizumab-for-the-treatment-of-recurrent-andor-metastatic-head-and-neck-squamous-cell-cancer-100582832","NCT06868433","TMV Vaccine Therapy Alone and With Pembrolizumab for the Treatment of Recurrent and\u002For Metastatic Head and Neck Squamous Cell Cancer","Phase 1b Study of TMV Vaccine Therapy Alone and TMV Vaccine Plus Pembrolizumab for Recurrent and\u002For Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)","Inclusion Criteria:\n\n* Must be at least ≥ 18 years of age\n* Histologically proven squamous cell carcinoma of the head and neck (HNSCC), amenable to salvage surgery. p16 positive and negative allowed. Squamous cell carcinoma of the oral cavity, larynx, hypopharynx, oropharynx, nasopharynx, sinonasal carcinoma and cancer of unknown primary (squamous cell carcinoma only) are all allowed. They will be allowed to have up to 3 different regimens after diagnosed of recurrent or metastatic HNSCC\n* Oropharyngeal tumors must have p16 or human papillomavirus (HPV) testing done\n* The tumor tissues must be available and banked (- 80°C) at the time of salvage surgery (1st informed consent form \\[ICF\\] must be signed)\n* Recurrent and\u002For metastatic HNSCC that has failed standard chemotherapy and immunotherapy. Eligible subjects must have progressed on ≥ 2 lines of standard of care prior to starting trial therapy. For patients who have relapsed within 6 months of systemic therapy given with curative intent, that therapy will count as a line of metastatic therapy. Eligible subjects will have no restriction on prior lines of therapy in the metastatic\u002Fadvanced disease setting\n* The tumors should be measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria\n* Must have enough tissue collected after salvage surgery to make at least 3 doses of vaccine (minimum weight of the resectable tumor tissue is ≥ .5 grams) and adequate cellularity (\\> 40% cellularity) assessed by the head and neck pathologists\n* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2\n* Absolute neutrophil count ≥ 1,500 cells\u002FuL\n* Platelets ≥ 100,000\u002FuL\n* Hemoglobin ≥ 9.0g\u002FdL (may receive packed red blood cell \\[prbc\\] transfusion)\n* Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN\n* Albumin ≥ 3.0 g\u002FdL\n* Serum creatinine ≤ 1.5 x ULN\n* Calculated creatinine clearance of ≥ 50 mL\u002Fmin\n* International normalized ratio (INR) ≤ 1.5. Anticoagulation is allowed only with low molecular weight heparin (LMWH). Patient receiving low molecular weight (LMW) heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level \\\u003C 1.1U\u002FmL are allowed on the trial\n* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures\n* Ability to understand and willingness to sign written informed consent documents\n* Female subjects of childbearing potential must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and 3 months after completion\n* Male subjects must agree to use adequate contraception (e.g., condoms; abstinence) for the duration of study treatment and 3 months after completion\n* Female subjects of childbearing age must have a negative serum pregnancy test at study entry\n* Patients who have received prior pembrolizumab are eligible\n\nExclusion Criteria:\n\n* Salivary tumors and non-squamous cell histology in head and neck cancer\n* Not enough tissue collected after surgery for a planned 3 doses (weight of the resectable tumor tissue is less than 1.0 gram)\n* Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)\n* Prior organ allograft or allogeneic bone marrow transplantation\n* Subjects with any active autoimmune disease or history of known or suspected autoimmune disease except for subjects with vitiligo, resolved childhood asthma\u002Fatopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll\n* Subjects with a condition requiring systemic treatment with either corticosteroids (\\> 10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \\> 10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease\n* Women who are pregnant or lactating, and child-bearing potential women without adequate contraception\n* Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association \\[NYHA\\] class III or IV), unstable angina pectoris, ventricular arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Other medications, or severe acute\u002Fchronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study\n* Clinical evidence of bleeding diathesis or coagulopathy\n* Patients with prior malignancies, including pelvic cancer, are eligible if they have been disease free for \\> 5 years. Patients with prior in situ carcinomas are eligible provided there was complete removal\n* Active bacterial or fungal infections requiring systemic treatment within 7 days of treatment\n* Use of other investigational drugs (drugs not marked for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration\n* History of severe hypersensitivity reactions to other monoclonal antibodies\n* Non-oncology vaccines within 28 days prior to planned treatment",{"count":609,"type":20},40,[76],"This phase Ib trial tests the safety, side effects and best dose of tumor membrane vesicle (TMV) vaccine therapy alone and in combination with pembrolizumab and evaluates how well it works in treating patients with head and neck squamous cell cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Vaccines made from a person's tumor cells, such as TMV vaccines, may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving TMV vaccine therapy alone or with pembrolizumab may be safe, tolerable and\u002For effective in treating patients with recurrent and\u002For metastatic head and neck squamous cell cancer.",[29,35,36,37,479,39,40,613,206,229,230,486,232,233,614,615,143,46,47,48,488,49,489],"Metastatic Sinonasal Squamous Cell Carcinoma","Recurrent Sinonasal Squamous Cell Carcinoma","Squamous Cell Carcinoma of Unknown Primary",[617],"Recurrent or metastatic head and neck cancer whose tumor should have banked at the time of surgery.","2026-03-02",{"date":620,"type":55},"2026-03-04",{"date":622,"type":55},"2025-05-08",{"date":213,"type":20},{"name":498,"class":183},{"id":626,"slug":627,"hasResults":11,"nctId":628,"briefTitle":629,"officialTitle":630,"acronym":4,"eligibilityCriteria":631,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":632,"targetDuration":4,"studyType":21,"phases":634,"briefSummary":635,"conditions":636,"keywords":4,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":638,"lastUpdatePostDateStruct":639,"startDateStruct":641,"completionDateStruct":643,"leadSponsor":644,"locationsCount":272},"100565019","phase-2-lovastatin-and-pembrolizumab-for-the-treatment-of-patients-with-recurrent-or-metastatic-head-and-neck-cancer-lapp-trial-100565019","NCT06636734","Lovastatin and Pembrolizumab for the Treatment of Patients With Recurrent or Metastatic Head and Neck Cancer, LAPP Trial","A Phase II Trial Of Lovastatin And Pembrolizumab In Patients With RM HNSCC (LAPP)","Inclusion Criteria:\n\n* Adult patients, male or female, aged ≥ 18, able to provide informed consent\n* Subjects with pathologically proven, recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) involving the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, or paranasal sinuses; patients with unknown primary HNSCC involving the cervical lymph nodes can be included if human papillomavirus (HPV)-positive\n* PD-L1 combined positive score (CPS) ≥ 1 (i.e., must be a candidate for treatment with pembrolizumab alone)\n* Patients must not be under consideration for salvage surgery\n* Measurable disease by RECIST 1.1 criteria\n* Life expectancy of more than 3 months, as determined by the investigator\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n* Recovery to baseline or ≤ grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5.0 from toxicities related to any prior treatments, unless adverse events are clinically non-significant and\u002For stable on supportive therapy\n* For men or women of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 8 weeks after the end of lovastatin\u002Fpembrolizumab administration\n* Absolute neutrophil count (ANC) ≥ 1000\u002Fmm\\^3 without colony stimulating factor support\n* Platelets ≥ 100,000\u002Fmm\\^3\n* Hemoglobin ≥ 9 g\u002FdL\n* Bilirubin ≤ 1.5 x the upper limit of normal (ULN). For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg\u002FdL\n* Serum albumin ≥ 2.8 g\u002Fdl\n* Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL\u002Fmin. For creatinine clearance estimation, the Cockcroft and Gault equation should be used\n* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 x ULN\n* Serum phosphorus, calcium, magnesium and potassium ≥ lower limit of normal (LLN)\n\nExclusion Criteria:\n\n* Patients already taking a statin drug\n* Liver dysfunction precluding the use of statins\n* Radiation to the head and neck or other sites within 4 weeks prior to enrollment\n* Cytotoxic chemotherapy or any form of investigational therapy within 4 weeks prior to study treatment\n* Prior treatment with immune checkpoint blocking therapy\n* Current use of drugs that interact with lovastatin (cimetidine, spironolactone, ketoconazole, and others)\n* Pregnancy, lactation, or plan to become pregnant\n* Inability to swallow lovastatin tablets\n* Known allergy or prior adverse reaction to lovastatin, other statin drugs, or pembrolizumab",{"count":633,"type":20},28,[23],"This phase II trial tests how well lovastatin and pembrolizumab work in treating patients with head and neck cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Lovastatin is a drug used to lower the amount of cholesterol in the blood and may also cause tumor cell death. In addition, studies have shown that lovastatin may make the tumor cells more sensitive to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lovastatin and pembrolizumab may kill more tumor cells in patients with recurrent or metastatic head and neck cancer.",[29,637,35,36,37,479,39,40,480,206,229,230,486,232,233,487,46,47,48,488,49,489],"Human Papillomavirus-Related Neck Squamous Cell Carcinoma of Unknown Primary","2026-02-08",{"date":640,"type":55},"2026-02-11",{"date":642,"type":55},"2024-12-09",{"date":213,"type":20},{"name":498,"class":183},{"id":646,"slug":647,"hasResults":11,"nctId":648,"briefTitle":649,"officialTitle":650,"acronym":4,"eligibilityCriteria":651,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":652,"targetDuration":4,"studyType":21,"phases":654,"briefSummary":655,"conditions":656,"keywords":4,"overallStatus":51,"whyStopped":4,"lastUpdateSubmitDate":659,"lastUpdatePostDateStruct":660,"startDateStruct":662,"completionDateStruct":664,"leadSponsor":666,"locationsCount":184},"100576227","phase-1-a-study-of-evofosfamide-in-combination-with-zalifrelimab-and-balstilimab-100576227","NCT06782555","A Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab","A Phase 1\u002F2 Immunotherapy Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab in Patients with Advanced Solid Malignancies","Inclusion Criteria:\n\n1. Histologically confirmed locally advanced or metastatic castration-resistant prostate cancer, pancreatic cancer, or HPV-negative SCCHN for which no other lines of standard therapy with demonstrated clinical benefit are available or appropriate as treatment.\n2. Appropriate to enter a clinical trial with a minimum estimated life expectancy of at least 3 months.\n3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n4. Measurable disease as defined by RECIST 1.1. Patients with castration-resistant prostate cancer can have measurable or evaluable disease per PCWG3 criteria. Patients with evaluable disease must have documented evidence of PD as defined by any of the following:\n\n   * PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least ≥4.0 ng\u002FmL.\n   * New or increasing non-bone disease per RECIST 1.1 criteria.\n   * Positive bone scan with 2 or more new lesions (PCWG3).\n5. Adequate bone marrow function as defined by the following laboratory test results obtained within 7 days of Cycle 1 Day 1:\n\n   * White blood cell count ≥2500 cells\u002Fmm3.\n   * Absolute neutrophil count ≥1500 cells\u002Fmm3.\n   * Absolute lymphocyte count \\>500 cells\u002Fmm3.\n   * Hemoglobin ≥9 g\u002FdL.\n   * Platelets ≥75,000 cells\u002Fmm3.\n6. Adequate liver function as defined by the following laboratory test results obtained within 7 days of Cycle 1 Day 1:\n\n   * Bilirubin ≤1.5 × institutional ULN; for patients with known Gilbert's syndrome, ≤3 × institutional ULN.\n   * Aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) ≤3 × institutional ULN; if liver metastases are present, then ≤5 × ULN is allowed.\n7. At least 3 weeks from previous cytotoxic chemotherapy or radiation therapy and at least 5 half-lives or 6 weeks, whichever is shorter, from targeted or biologic therapy with the exception of CTLA-4, PD-1, or PD-L1 blocking antibodies for which only a 2 week interval is required. Patients with prostate cancer, unless they have undergone prior orchiectomy, may continue to receive androgen deprivation therapy, anti-androgen therapy, or therapy that interferes with androgenic stimulation.\n8. All patients must be willing to undergo a biopsy to provide a new tumor sample within 14 days of Cycle 1 Day 1. Patients who are unable to undergo a biopsy at screening must submit archival tumor tissue retrieved within the last 6 calendar months. Patients must also consent to undergo a biopsy between Day 15 of Cycle 2 and Day 8 of Cycle 3 in those subjects which it is clinically safe and attainable. A biopsy is not required for participants with metastatic prostate cancer with bone-only disease or inaccessible soft tissue lesions.\n9. Calculated creatinine clearance ≥ 60 mL\u002Fmin (by the Cockcroft Gault formula) within 7 days of Cycle 1 Day 1\n\nExclusion Criteria:\n\n1. A history of currently active\u002Funcontrolled autoimmune diseases or disorders, including inflammatory bowel disease (including Crohn's disease and ulcerative colitis), rheumatoid arthritis, systemic sclerosis (scleroderma), systemic lupus erythematosus, or autoimmune vasculitis (eg, Wegener's granulomatosis).\n2. Patients with prior history of any Grade 3 or Grade 4 AEs from anti-CTLA-4, anti-PD-1\u002FPD-L1, or anti-CTLA-4 and anti-PD-1\u002FPD-L-1 combination therapy.\n3. History of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis, or other known risk factors for bowel perforation.\n4. Patients on long-term systemic steroids (\\>10 mg daily prednisone equivalent initiated \\>2 weeks prior to study enrollment). Inhaled or topical steroids are permitted in the absence of active autoimmune disease.\n5. Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study treatment hazardous or obscure the interpretation of AEs, e.g., a condition associated with frequent diarrhea or chronic skin conditions, recent surgery (within 30 days) or colonic biopsy from which the patient has not recovered, partial endocrine organ deficiencies, or substance abuse.\n6. Concomitant use of QT-prolonging drugs with a risk of causing Torsades de Pointes (TdP).\n7. History of risk factors for TdP, including family history of long QT syndrome.\n8. Corrected QT (QTc) interval of ≥470 msec calculated according to Fridericia's formula (QTc=QT\u002FRR \\[0.33\\]).\n9. Sustained systolic blood pressure (BP) \\>140 mmHg or \\\u003C90 mmHg and sustained diastolic BP \\>100 mmHg or \\\u003C60 mmHg.\n10. Patients with newly diagnosed, uncontrolled and\u002For untreated cancer-related central nervous system disease. Patients with treated brain metastases that are radiographically or clinically stable for at least 2 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion(s) are eligible if they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to study enrollment).\n11. Uncontrolled intercurrent illness including, but not limited to, myocardial infarction within 6 months, unstable symptomatic ischemic heart disease, significant cardiac arrythmias, active uncontrolled infection requiring systemic therapy, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n12. Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to study enrollment.\n13. Current evidence of active and uncontrolled infection, New York Heart Association Class III-IV chronic heart failure, documented Child's class B and C cirrhosis, active symptomatic pancreatitis, or uncontrolled medical disease which, in the opinion of the investigator, could compromise assessment of study treatment efficacy.\n14. Active human immunodeficiency virus infection (Exception: patients with well-controlled HIV \\[e.g., CD4 ≥ 350 cells\u002FuL and undetectable viral load\\] who have been on an effective (drug, dosage, and schedule associated with reduction and control of the viral load) antiretroviral therapy (ART) for ≥ 4 weeks are eligible). Patients with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last 12 months are not eligible. Note: Drug-drug interactions with ART occur via many mechanisms, with cytochrome P450 CYP3A4-mediated interactions being the most common. Patients who are using concurrent strong or moderate CYP3A4 inhibitors (e.g., ritonavir, cobicistat) or strong or moderate CYP3A4 inducers must be switched to an alternate effective ART regimen ≥ 4 weeks before study enrollment or should be excluded from the study if their regimen cannot be altered.\n15. Active or chronic hepatitis B or C virus infection. Patients with a history of HCV infection must have completed curative antiviral treatment and must have a viral load below the limit of quantification. A patient who is HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution is eligible.\n16. Known hypersensitivity to any components of the study treatment or any of their excipients or analogs or drugs of similar chemical or biologic composition.\n17. Live vaccine within 4 weeks prior to study enrollment.\n18. Concomitant therapy with interleukin-2, interferon, or other non-study immunotherapy agents, or immunosuppressive agents.\n19. Concomitant use of strong or moderate inhibitors or strong or moderate inducers of CYP3A4 within 14 days or 5 half-lives (whichever is longer) prior to study enrollment and for the duration of study treatment.\n20. Concomitant use of anti-cancer chemotherapy, radiotherapy, hormone therapy, or targeted therapy. Patients with prostate cancer may continue treatment with anti-androgen and bone targeted therapies (e.g., zoledronic acid and denosumab). Palliative radiotherapy to nontarget lesions is permitted.",{"count":653,"type":20},71,[76,23],"The purpose of this Phase 1\u002F2 study is to test the overall safety, tolerability, and effectiveness of the combination investigational drugs evofosfamide, zalifrelimab, and balstilimab in treating advanced or metastatic castration-resistant prostate cancer, pancreatic cancer, and human papilloma virus (HPV)-negative squamous cell carcinoma of the head and neck (SCCHN).",[657,35,658],"Metastatic Prostate Cancer","Metastatic Pancreatic Cancer","2025-01-17",{"date":661,"type":55},"2025-01-21",{"date":663,"type":55},"2025-01-08",{"date":665,"type":20},"2028-01",{"name":667,"class":377},"ImmunoGenesis"]