[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"advanced-head-and-neck-squamous-cell-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:advanced-head-and-neck-squamous-cell-carcinoma":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,45,87,144],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100600222","phase-2-ivonescimab-before-surgery-for-the-treatment-of-resectable-stage-ii-iv-head-and-neck-cancer-100600222",false,"NCT07094685","Ivonescimab Before Surgery for the Treatment of Resectable Stage II-IV Head and Neck Cancer","A Phase II Study Evaluating Neoadjuvant Ivonescimab for Resectable Head and Neck Cancer","SENIOR-HN","Inclusion Criteria:\n\n* At least 18 years of age\n* PD-L1 combined positive score (CPS) \\>= 1\n* Histologically documented advanced stage mucosal HNSCC (stage II-IV), for which surgery would be recommended in routine clinical practice\n* Primary tumor is amenable to fresh biopsy or availability of archival fresh frozen primary tissue\n* Eastern Cooperative Oncology Group (ECOG) 0-1\n* Absolute neutrophil count \\> 1500 cells\u002FuL\n* Platelet count \\>= 100,000\u002FuL\n* Hemoglobin \\>= 9.0 g\u002FdL (without transfusion within 14 days prior to cycle 1, day 1)\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN) or =\\\u003C 3 x ULN for participants with Gilbert's disease\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\\\u003C 2.5 x institutional ULN\n* Creatinine =\\\u003C 1.5 x institutional ULN OR estimated glomerular filtration rate (eGFR) value \\>= 30\u002FmL using the Chronic Kidney Disease Epidemiology (CKD-EPI) equation OR measured (OR calculated) creatinine clearance \\>= 50 mL\u002Fmin using the Cockcroft-Gault Formula\n* Urine protein \\\u003C 2+ or 24-hour urine protein quantification \\\u003C 1.0 g\n* Prothrombin time (PT) or international normalized ratio (INR) =\\\u003C 1.5 x ULN, and partial thromboplastin time (PTT) or activated (a)PTT =\\\u003C 1.5 x ULN (unless abnormalities are unrelated to coagulopathy) This applies only to patients who are not on therapeutic anti-coagulation\n\n  * For patients receiving therapeutic anti-coagulation there are no coagulation parameters for eligibility. However, patients should be on a stable dose\n* Female patients of childbearing age per institutional definition must have negative serum pregnancy test results before enrollment\n* Female patients of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 90 days after the last dose of ivonescimab\n* Unsterilized male patients having sex with a female partner of childbearing potential, or a pregnant or breastfeeding partner must agree to use barrier contraception (male condom) for the duration of the treatment period until 90 days after the last dose of ivonescimab. Male patients with female partners of childbearing potential must have the female partner agree to use at least 1 form of highly effective contraception for the duration of the treatment period until 90 days after the last dose of ivonescimab\n* Ability to understand and the willingness to sign a written informed consent\n* Deemed to be a candidate for trial therapy by University of Michigan providers in both Medical Oncology and Otolaryngology or Oral and Maxillofacial Surgery\n\nExclusion Criteria:\n\n* Prior radiation therapy for treatment of the current mucosal HNSCC (patients undergoing salvage resection are excluded)\n* Prior neck dissection on the side of current mucosal HNSCC\n* Major surgical procedures or serious trauma within 4 weeks prior to enrollment. Minor local procedures (excluding central venous catheterization, port implantation, and tumor biopsy) within 3 days prior to planned cycle 1, day 1\n* History of bleeding tendencies or coagulopathy and\u002For clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment\n* Nasal bleeding \u002F epistaxis (bloody nasal discharge is allowed) graded as \\>= grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 within 14 days prior to registration\n* Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to enrollment is not allowed. The use of full-dose anticoagulants is permitted as long as INR or aPTT is within therapeutic limits\n* Patients with a condition requiring corticosteroid therapy (\\> 10 mg prednisone\u002Fday or equivalent) within 14 days of the first dose of study drug. Exceptions: Physiologic replacement doses are allowed even if they are \\> 10 mg of prednisone\u002Fday or equivalent, as long as they are not being administered for immunosuppressive intent. Inhaled or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder\n* Patients with active, known, or suspected autoimmune disease that has required systemic therapy within 5 years of the projected enrollment date. Exceptions: Patients with vitiligo, type I diabetes mellitus, and endocrinopathies (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement, childhood asthma that has resolved, or psoriasis that does not require systemic treatment are permitted\n* Patients with symptomatic central nervous system (CNS) metastases, CNS metastases with hemorrhagic features, CNS metastasis \\>= 1.5 cm, CNS radiation within 7 days prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease\n* Recipient of a solid organ or allogeneic stem cell transplant\n* Patients with active hepatitis B (Patients with stable or declining levels of hepatitis B deoxyribonucleic acid \\[DNA\\] by polymerase chain reaction \\[PCR\\] on appropriate anti-viral therapy with acceptable tolerability for one month prior to enrollment will not be excluded)\n* Patients with active hepatitis C (hepatitis C virus \\[HCV\\] antibody positive with HCV ribonucleic acid \\[RNA\\] levels above the lower limit of detection)\n* Known allergy or hypersensitivity to any component of the study drug or any excipients (histidine, histidine hydrochloride, sucrose, polysorbate 80 (II), and water for injection); known history of severe hypersensitivity to other monoclonal antibodies\n* Patient is breastfeeding or plans to breastfeed during study participation\n* Radiographic evidence of major blood vessel encasement with narrowing of the vessel that the investigator determines will pose a significantly increased risk of bleeding\n* Live vaccine or live attenuated vaccine received within 4 weeks prior to planned enrollment or scheduled to receive a live vaccine or live attenuated vaccine during the study period. Inactivated vaccines are permitted\n* History of non-infectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease\n* Has pre-existing peripheral neuropathy that is \\>= grade 2 by CTCAE version 5\n* History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before enrollment\n* Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before enrollment\n* History of perforation of the gastrointestinal tract and\u002For fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to enrollment\n* Known history of human immunodeficiency virus (HIV) whose viral load is not controlled\n* Participant has active cardiovascular disease including, but not limited to:\n\n  * Thromboembolism\n\n    * Medical history of any grade arterial thromboembolic event, grade 3 and above venous thromboembolic event (as specified in NCI CTCAE 5.0)\n  * Cardiovascular disease\n\n    * Any of the following within 12 months prior to enrollment:\n\n      * Myocardial infarction\n      * Unstable angina\n      * Unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease)\n      * Transient ischemic attack\n      * Cerebrovascular accident\n      * Hypertensive Crisis\n      * Hypertensive encephalopathy\n      * Coronary stent placement\n    * Clinically non-significant thrombosis, such as non-obstructive catheter-associated thrombus, incidental or asymptomatic pulmonary embolism, are not exclusionary\n  * Hypertension\n\n    * Uncontrolled (persistent) hypertension:\n\n      * Systolic blood pressure \\> 160 mmHg; diastolic blood pressure \\> 100 mmHg\n  * Heart failure\n\n    * Congestive heart failure (CHF), defined as New York Heart Association (NYHA) class III-IV or hospitalization for CHF within 12 months prior\n* Participant has uncontrolled illness including, but not limited to:\n\n  * Severe infection within 4 weeks prior to enrollment, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection (as determined by the investigator) requiring systemic anti-infective therapy within 2 weeks prior to enrollment (excluding antiviral therapy for hepatitis B or C)\n  * Uncontrolled diabetes\n  * Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy)\n  * Psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements\n  * Active bleeding diathesis requiring anticoagulant or antiplatelet therapy","ALL","18 Years",{"count":20,"type":21},28,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","This phase II trial tests how well ivonescimab before surgery works in treating patients with stage II-IV head and neck cancer that can be removed by surgery (resectable). Ivonescimab is a bispecific monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A bispecific monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens).",[27,28,29,30,31],"Advanced Head and Neck Squamous Cell Carcinoma","Resectable Head and Neck Squamous Cell Carcinoma","Stage II Head and Neck Cutaneous Squamous Cell Carcinoma","Stage III Head and Neck Cutaneous Squamous Cell Carcinoma","Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma","RECRUITING","2026-06-23",{"date":35,"type":36},"2026-06-26","ACTUAL",{"date":38,"type":36},"2025-11-18",{"date":40,"type":21},"2030-11-01",{"name":42,"class":43},"University of Michigan Rogel Cancer Center","OTHER",1,{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":4,"eligibilityCriteria":51,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":52,"targetDuration":4,"studyType":22,"phases":54,"briefSummary":56,"conditions":57,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":78,"lastUpdatePostDateStruct":79,"startDateStruct":81,"completionDateStruct":83,"leadSponsor":85,"locationsCount":44},"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":53,"type":21},160,[55],"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.",[58,27,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77],"Advanced Biliary Tract Carcinoma","Advanced Hepatocellular Carcinoma","Advanced Lung Non-Small Cell Carcinoma","Advanced Malignant Solid Neoplasm","Advanced Melanoma","Advanced Renal Cell Carcinoma","Metastatic Biliary Tract Carcinoma","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Malignant Solid Neoplasm","Metastatic Melanoma","Metastatic Renal Cell Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","Stage III Hepatocellular Carcinoma AJCC v8","Stage III Lung Cancer AJCC v8","Stage III Renal Cell Cancer AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IV Lung Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","2026-06-10",{"date":80,"type":36},"2026-06-12",{"date":82,"type":36},"2026-06-08",{"date":84,"type":21},"2028-12-31",{"name":86,"class":43},"OHSU Knight Cancer Institute",{"id":88,"slug":89,"hasResults":11,"nctId":90,"briefTitle":91,"officialTitle":92,"acronym":4,"eligibilityCriteria":93,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":94,"targetDuration":4,"studyType":22,"phases":96,"briefSummary":98,"conditions":99,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":135,"lastUpdatePostDateStruct":136,"startDateStruct":138,"completionDateStruct":140,"leadSponsor":142,"locationsCount":44},"100442316","phase-1-iacs-6274-with-or-without-bevacizumab-and-paclitaxel-for-the-treatment-of-advanced-solid-tumors-100442316","NCT05039801","IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors","A Phase 1 Open-Label, Dose-Escalation and Dose-Expansion Study to Investigate the Safety, Pharmacokinetics, and Anti-Tumor Activity of IACS-6274 as Monotherapy and in Combination in Patients With Advanced Solid Tumors","Inclusion Criteria All Parts\n\n1. Provision of written informed consent prior to any study related procedures and compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n2. Male or female patients ≥18 years of age at the time of study entry who agree to participate by giving written informed consent prior to participation in any study related activities.\n3. Histologically or cytologically confirmed advanced solid tumors, specifically:\n\n   Dose Escalation for Part A may include:\n\n   Patients with tumors harboring actionable KEAP1\u002FNFE2L2\u002FSTK11\u002FNF1 mutations Patients with low ASNS expression levels (HGSOC or endometrial cancer) Patients who had immunotherapy (IO) melanoma (Minimum treatment duration of prior PD-1 or PD-L1-containing regimen of 12 weeks \\[or equivalent of 2 response evaluations\\]).\n\n   Patients with post-platinum HNSCC Patients with chondrosarcoma Patients with ARID1A mutant clear cell ovarian cancer\n\n   Dose Escalation for Part B may include:\n\n   Confirmed recurrent high-grade non-mucinous ovarian cancer that is platinum-resistant, defined as disease relapse within a platinum-free interval (PFI, or the time elapsed from the last date of platinum dose until PD) of \\\u003C 6 months, and with less than 5 prior therapies\n\n   Dose Expansion for Part B limited to:\n\n   Confirmed recurrent high-grade non-mucinous ovarian cancer with low ASNS expression levels that is platinum-resistant, defined as disease relapse within a PFI of \\\u003C 6 months, and with less than 5 prior therapies.\n\n   Dose Escalation for Part C may include:\n\n   Patients with tumors harboring actionable KEAP1\u002FNFE2L2 mutations Patients with tumors harboring PIK3CA hotspot mutations, activating AKT mutations, and inactivating PTEN mutations (irrespective of KEAP1\u002FNFE2L2 mutations) Patients with low ASNS expression levels (HGSOC)\n\n   Dose Expansion for Part C limited to:\n\n   Patients with NSCLC with actionable KEAP1\u002FNFE2L2 mutations Patients with HGSOClow ASNS expression levels (irrespective of biomarker status for KEAP1\u002FNFE2L2)\n4. Patients must have received at least one line of therapy for advanced stage disease and be refractory or ineligible to available existing therapy(ies) known to provide clinical benefit for their condition.\n5. Prior treatment with chemotherapy, radiotherapy, immunotherapy or any investigational therapies must have been completed at least 3 weeks or at least five half lives, whichever is shorter, before the study drug administration, and all AEs (excluding alopecia and peripheral neuropathy) have either returned to ≤Grade 1 or stabilized. Patients with concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) are allowed.\n6. Fresh and\u002For archival tumor tissue from a biopsy obtained between the completion of the most recent line of treatment until study entry must be available for mutation and biomarker analysis. If available, archival tumor tissue from the time of initial diagnosis or the most recent biopsy (archival and\u002For fresh) will be collected. For ovarian cancer patients, a fresh biopsy must be collected in addition to archival tumor tissue. NOTE: No fresh tumor tissue will be required if a previous biopsy detected the selected mutations for each cohort. In all cases, procedures to obtain fresh tumor tissue should not put the patient at undue risk, and should only be performed if the risk is minimal (no greater than 2% risk of serious or severe complications).\n7. Patients must have at least 1 lesion (measurable and\u002For non-measurable) that can be accurately assessed at baseline by CT or MRI and is suitable for repeated assessments.\n8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.\n9. Adequate organ function as indicated by the following laboratory values:\n\n   Absolute neutrophil count (ANC) ≥1.0×109\u002FL Platelets ≥100×109\u002FL Hemoglobin ≥9.0 g\u002FdL (\\>5.59 mmol\u002FL) Creatinine clearance (CrCl) \\>50 mL\u002Fmin. Actual body weight should be used for calculating creatinine clearance using the Cockroft Gault equation (except for patients with body mass index \\>30 kg\u002Fm2 when the lean body weight should be used, and without the need for chronic dialysis therapy).\n\n   Serum total bilirubin ≤1.5×ULN (with the exception of patients with known thalassemia minor mutations or Gilbert's syndrome: serum total bilirubin must be \\\u003C3×ULN in these patients) Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤2.5×ULN or ≤5×ULN for patients with liver metastases)\n10. Adequate cardiac function with a left ventricular ejection fraction ≥50%\n11. Female patients of non childbearing potential, who are physiologically incapable of becoming pregnant, are eligible to enter and participate in the study if they:\n\n    have had a hysterectomy, OR have had a bilateral oophorectomy, OR have had a bilateral salpingectomy, OR is postmenopausal (total cessation of menses for ≥2 years, or follicle stimulating hormone ≥50 IU\u002FL).\n12. Female patients of childbearing potential, who are not post-menopausal or surgically sterile and intent to be sexually active with a non-sterile male partner, are required to use one form of highly effective contraception combined with a barrier method (male condom, female condom, cervical cap, diaphragm with spermicide, or contraceptive sponge with spermicide) of contraception starting before entering the study and until 4 weeks after the last dose of treatment.\n\n    Highly effective non-hormonal contraceptive methods that are acceptable include:\n\n    Total\u002Ftrue abstinence\\*\\*\\* for the total duration of the study treatment and for at least 1 month after the last dose of study treatment. Periodic abstinence using methods such as calendar ovulation, symptothermal, post ovulation methods, declaration of abstinence solely for the duration of a trial, or withdrawal are not acceptable methods of contraception.\n\n    Having a vasectomized sexual partner, who received post-vasectomy confirmation of azoospermia, combined with a barrier method as described above.\n\n    Bilateral tubal occlusion combined with a barrier method as described above. Intrauterine device with copper banded coils, combined with a barrier method as described above.\n\n    Highly effective hormonal contraceptive methods that are acceptable include:\n\n    Combined oral pill contraception (normal and low-dose oral pills, or progesterone-based oral pills using desogestrel) combined with a barrier method as described above. NOTE: cerazette is currently the only highly efficacious progesterone-based pill available.\n\n    Injection (e.g., medroxyprogesterone) combined with a barrier method as described above.\n\n    Patch (e.g., norelgestromin or ethinyl estradiol transdermal system) combined with a barrier method as described above.\n\n    Implants (etonorgestrel-releasing) combined with a barrier method as described above.\n\n    Intravaginal device (e.g., ethinyl estradiol- or etonogestrel-releasing) combined with a barrier method as described above.\n\n    Intrauterine system (levonorgestrel-releasing) combined with a barrier method as described above.\n\n    In addition to the to use one form of highly effective contraception combined with a barrier method, female patients of childbearing potential must have a negative serum pregnancy test at screening (within 7 days of the start of treatment) and must not be breastfeeding.\n13. Non-sterile men, who are not sexually abstinent and intend to be sexually active with a woman of childbearing potential, must use a condom from the start of the trial and until 16 weeks after the last dose of treatment, or must practice total abstinence\\*\\*\\* for the total duration of the study treatment and at least 3 months after the last dose of study treatment. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female partners of childbearing potential should consider the use of at least one contraception method describe above. If the female partner is pregnant, male participants should use a condom plus spermicide.\n\n    * Total\u002Ftrue abstinence is defined as a patient who refrains from any form of sexual intercourse, and this is in line with their usual and\u002For preferred lifestyle.\n\nExclusion Criteria All Parts\n\n1. Prior malignancy within the previous 2 years except for locally curable cancers that have been cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the cervix, breast or bladder.\n2. Known primary central malignancy or symptomatic central nervous system metastasis(es).\n\n   Note: Patients with stable, previously treated brain metastases may participate if neurologic symptoms have resolved, patients have been off steroids (at least 7 days for Part A and Part B, and at least 4 weeks for Part C), and there is no evidence of disease progression by imaging for at least 2 weeks before the first dose of study treatment.\n3. Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following cardiac conditions:\n\n   1. Any unstable cardiac arrhythmia within 6 months prior to enrolment\n   2. Prolongation of the Fridericia corrected QT (QTcF) interval defined as \\>450 ms for males and \\>470 ms for females\n   3. History of any of the following cardiovascular conditions within 6 months of enrolment:\n\n      * cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association.\n4. Major surgical intervention within 28 days before study drug administration, or an anticipated need for major surgery during the study.\n5. Significant acute or chronic infections.\n6. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.\n7. Treatment with strong cytochrome P450 subtype 3A4 (CYP3A4) inducers and inhibitors (including grapefruit juice) within 2 weeks of the first dose of study drug NOTE: patients must have stopped taking St. John's Wort 3 weeks prior to the start of treatment and stopped taking enzalutamide 4 weeks prior to the start of treatment.\n8. Treatment with strong CYP450 subtype 2D6 (CYP2D6) inhibitors or sensitive CYP3A4 substrates within 7 days of the first dose of study drug.\n9. Radiotherapy within 4 weeks prior to the start of study drug. Palliative radiotherapy for symptomatic control is acceptable if completed at least 2 weeks prior to study drug administration and no additional radiotherapy for the same lesion is planned.\n10. Underlying medical conditions (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant and active bleeding diseases), for which in the investigator's opinion will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or AEs.\n11. History of allergic reactions attributed to compounds of similar chemical or biological composition to any of the compounds in the study.\n12. Known history of alcohol or drug abuse.\n13. Legal incapacity or limited legal capacity.\n14. Inability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation. Patients should not have gastrointestinal illnesses (such as refractory nausea and vomiting, chronic gastrointestinal disease or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretionof IACS-6274 and capivasertib, which are oral agents.\n15. Patients unwilling to comply with protocol requirements related to the assigned part.\n16. Any other disease, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.\n\nPart B Specific Exclusion Criteria (B1) Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, three or more features of partially controlled asthma).\n\n(B2) Patient has a known hypersensitivity to paclitaxel or bevacizumab components or excipients.\n\n(B3) Patient has a history of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.\n\n(B4) Patient has proteinuria as demonstrated by urine protein:creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate \\\u003C2 g of protein in 24 hours to be eligible).\n\n(B5) Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).\n\n(B6) Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident \\[CVA\\]) within 6 months of enrollment. (B7) Patient has pre-existing peripheral neuropathy that is Grade ≥2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria.\n\n(B8) Patient requires paracentesis 2 weeks prior to trial enrolment. Part C Specific Exclusion Criteria (C1) History of another primary malignancy, except for a malignancy treated with curative intent, with no known active disease ≥5 years before the first dose of treatment, with low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy.\n\n(C2) Patient has a known hypersensitivity to capivasertib components or any excipients of the product.\n\n(C3) Clinically significant abnormalities of glucose metabolism as defined by any of the following: Diagnosis of diabetes mellitus type I or II (irrespective of management), Glycosylated haemoglobin (HbA1c) \\>8% (64 mmol\u002Fmol) (C4) Patients with evidence of severe or uncontrolled systemic liver disease including severe hepatic impairment, or abnormal liver enzymes at screening (AST or ALT \\>2.5 x ULN; total bilirubin \\>1.5 x ULN).\n\n(C5) Patients with elevated alkaline phosphatase (ALP) can be enrolled if the abnormal value is due to the presence of bone metastasis, but liver function is considered adequate according to the principal investigator.\n\n(C6) Patients with persistent toxicities (Grade ≥2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study treatment may be included after consultation with the sponsor and the study physician.\n\n(C7) Patients with spinal cord compression or leptomeningeal disease not requiring steroids for at least 4 weeks prior to start of study intervention.\n\n(C8) Patients with clinically significant cardiovascular disease including, but not limited to, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident \\[CVA\\]) within 6 months of enrollment. In addition, patients will be excluded based on the study physician's judgment of the following criteria:\n\n* Mean resting corrected QT interval \\>470ms, obtained from triplicate ECGs performed at screening.\n* Medical history significant for arrhythmia that is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation regardless of treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be included based on the study physician's judgment.\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia of Grade ≥1, potential for Torsades de Pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first-degree relative, history of QT prolongation associated with other medications that required discontinuation of the medication.\n* Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association Grade ≥2.\n* Uncontrolled hypotension: SBP \\\u003C90 mmHg and\u002For DBP \\\u003C50 mmHg.\n* Cardiac ejection fraction outside institutional range of normal or \\\u003C50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition \\[MUGA\\] scan if an echocardiogram cannot be performed or is inconclusive).\n\n(C9) Patients with active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice) are excluded.\n\n(C10) Patients with active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening are excluded.\n\nHuman immunodeficiency virus (HIV) positive patients with a viral load \\> 400 copies\u002FmL and a CD4+ T-cell count of \\\u003C350 cells\u002FuL or with a history of an acquired immunodeficiency syndrome (AIDS) opportunistic infection within the past 12 months are excluded. Patients with a higher viral load or lower CD4+ count (\\\u003C 350 cells\u002FuL) may be considered for eligibility if the patient has a potentially curable malignancy or for interventions in a later stage of development that have demonstrated prior activity with a given cancer.\n\nHIV-positive patients receiving antiretroviral therapies should be on established ART for at least four weeks before starting treatment to ensure that treatment is tolerated and that toxicities are not confused with investigational drug toxicities. HIV-positive patients receiving antiretroviral therapies that are strong CYP3A4\u002F5 inhibitors\u002F inducers or sensitive substrates of CYP3A4 will be excluded due to the potential for drug-drug interaction with capivasertib.\n\n(C12) Patients who are undergoing any concurrent anticancer treatment or any concomitant medication that may interfere with the study drugs according to local clinical guidelines are excluded.\n\n(C13) Patients who received palliative radiotherapy within 2 weeks prior to the start of study treatment; or radiotherapy to more than 30% of the bone marrow within 4 weeks before the start of study treatment are excluded.",{"count":95,"type":21},54,[97],"PHASE1","To find the highest tolerable dose of IACS-6274 that can be given alone, in combination with bevacizumab and paclitaxel, or in combination with capivasertib to patients who have solid tumors. The safety and tolerability of the study drug(s) will also be studied.",[100,27,61,62,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134],"Advanced Endometrial Carcinoma","Advanced Ovarian Clear Cell Adenocarcinoma","Chondrosarcoma","Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Pathologic Stage III Cutaneous Melanoma AJCC v8","Pathologic Stage IIIA Cutaneous Melanoma AJCC v8","Pathologic Stage IIIB Cutaneous Melanoma AJCC v8","Pathologic Stage IIIC Cutaneous Melanoma AJCC v8","Pathologic Stage IIID Cutaneous Melanoma AJCC v8","Pathologic Stage IV Cutaneous Melanoma AJCC v8","Recurrent Ovarian High Grade Serous Adenocarcinoma","Refractory Endometrial Carcinoma","Refractory Head and Neck Squamous Cell Carcinoma","Refractory Melanoma","Refractory Ovarian Clear Cell Adenocarcinoma","Refractory Ovarian High Grade Serous Adenocarcinoma","Stage III Ovarian Cancer AJCC v8","Stage III Uterine Corpus Cancer AJCC v8","Stage IIIA Ovarian Cancer AJCC v8","Stage IIIA Uterine Corpus Cancer AJCC v8","Stage IIIA1 Ovarian Cancer AJCC v8","Stage IIIA2 Ovarian Cancer AJCC v8","Stage IIIB Ovarian Cancer AJCC v8","Stage IIIB Uterine Corpus Cancer AJCC v8","Stage IIIC Ovarian 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 Ovarian Cancer AJCC v8","Stage IV Uterine Corpus Cancer AJCC v8","Stage IVA Ovarian Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Ovarian Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8","2026-05-29",{"date":137,"type":36},"2026-06-01",{"date":139,"type":36},"2021-09-30",{"date":141,"type":21},"2028-06-30",{"name":143,"class":43},"M.D. Anderson Cancer Center",{"id":145,"slug":146,"hasResults":11,"nctId":147,"briefTitle":148,"officialTitle":149,"acronym":4,"eligibilityCriteria":150,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":151,"targetDuration":4,"studyType":22,"phases":153,"briefSummary":154,"conditions":155,"keywords":162,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":179,"lastUpdatePostDateStruct":180,"startDateStruct":182,"completionDateStruct":184,"leadSponsor":186,"locationsCount":189},"100509238","phase-1-a-phase-ibii-study-of-an-anti-her3-antibody-hmbd-001-with-cetuximab---docetaxel-in-advanced-squamous-cell-cancers-100509238","NCT05910827","A Phase Ib\u002FII Study of an Anti-HER3 Antibody, HMBD-001, With Cetuximab +\u002F- Docetaxel in Advanced Squamous Cell Cancers","A Phase Ib\u002FII Study to Evaluate HMBD-001 in Combination With Cetuximab, With or Without Docetaxel in Participants With Advanced Squamous Cell Carcinomas","Inclusion Criteria:\n\n* Ability to understand and be willing to sign an informed consent form\n\n  * Males and females aged over 18 years (or having reached the age of majority according to local laws if the age of majority is \\> 18 years of age)\n  * Eastern Cooperative Oncology Group (ECOG) status of 0 to 1\n  * Arm B only: Locally advanced or metastatic squamous non-small cell lung cancer for which all available standard of care treatment options have been exhausted or refused and for which at least one lesion is measurable\n  * Arm C only: Advanced or metastatic sqNSCLC, HNSCC, ESCC, CSCC, cervical SCC, NPC and other SCCs with at least one prior line of systemic therapy,\n  * Have an estimated life expectancy of at least 3 months\n  * Participants must be willing to provide a fresh tumor biopsy sample\n  * Have adequate organ function\n  * Females must be non-pregnant and non-lactating, willing to use a highly effective method of contraception from screening until study completion or be either surgically sterile or post-menopausal\n  * Males must be surgically sterile, abstinent, or if engaged in sexual relations with a woman of child-bearing potential, the participant and his partner must be surgically sterile or using an acceptable, highly effective contraceptive method from screening until study completion\n\nExclusion Criteria:\n\n* Prior treatment with HMBD-001, docetaxel, cetuximab or any other agent that targets Epidermal Growth Factor Receptor (EGFR) or HER3, including pan-HER inhibitors. Prior treatment with docetaxel is allowed for Arm C\n\n  * Receipt of prior targeted therapy, including but not limited to those targeting EGFR activating mutations, ALK fusions, ROS rearrangements, RET fusions or mutations, BRAF V600E mutation, MET exon 14 skipping mutation, and\u002For KRAS G12C mutation\n  * Persistent clinically significant toxicities (Grade ≥2) from previous anti-cancer therapy except for Grade \\>2 toxicities that are considered unlikely to put the participant at an increased risk of treatment-related toxicity and\u002For impact the study results e.g., alopecia\n  * Most recent anti-cancer therapy including radiotherapy at least 4 weeks, or nitrosourea or mitomycin 3 at least 6 weeks, or 5 half-lives whichever is shorter prior to starting the assigned study treatment\n  * Symptomatic primary Central Nervous System (CNS) cancer or metastases unless the symptoms are stable for at least 28 days prior to the first dose of the study drug and any symptoms have returned to baseline\n  * Evidence of abnormal cardiac function\n  * History of uncontrolled allergic reactions and\u002For known expected hypersensitivity to the study drugs used in the treatment arm to which the participant is to be enrolled into\n  * Any other known active malignancy except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer\n  * Any uncontrolled illness or significant uncontrolled condition(s) requiring systemic treatment\n  * Known Human Immunodeficiency Virus (HIV) infection\n  * Active hepatitis B or hepatitis C infection\n  * Pregnant or breast feeding\n  * COVID 19 infection within 3 months prior to the first dose of the study drug\n  * COVID 19 vaccination within 14 days prior to the first dose of the study drug\n  * Treatment with strong inhibitors or inducers of CYP3A4",{"count":152,"type":21},398,[97,24],"This is a Phase Ib\u002FII multi-center, open-label study of HMBD-001 in combination with cetuximab with or without docetaxel in participants with advanced Squamous Cell Cancers",[156,27,157,158,159,160,161],"Advanced or Metastatic Squamous Non-Small Cell Lung Cancer","Advanced Esophageal Squamous Cell Carcinoma","Cervical Squamous Cell Carcinoma","Advanced Cutaneous Squamous Cell Carcinoma","Nasopharyngeal Cancinoma (NPC)","Squamous Cell Carcinoma",[163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178],"NSCLC","Non-small Cell Lung Cancer","sqNSCLC","Lung","Squamous","HER3","ErbB3","Docetaxel","Cetuximab","cervical squamous cell carcinoma","HNSCC","CSCC","ESCC","advanced squamous cell cancer","NPC","SCC","2026-05-24",{"date":181,"type":36},"2026-05-27",{"date":183,"type":36},"2024-02-05",{"date":185,"type":21},"2027-12",{"name":187,"class":188},"Hummingbird Bioscience","INDUSTRY",20]