[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-microsatellite-stable-colorectal-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-microsatellite-stable-colorectal-carcinoma":31},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,47,69,98],{"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":25,"conditions":26,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":35,"lastUpdatePostDateStruct":36,"startDateStruct":39,"completionDateStruct":41,"leadSponsor":43,"locationsCount":46},"100492388","phase-1-testing-the-combination-of-the-anti-cancer-drugs-temozolomide-and-m1774-to-evaluate-their-safety-and-effectiveness-100492388",false,"NCT05691491","Testing the Combination of the Anti-Cancer Drugs Temozolomide and M1774 to Evaluate Their Safety and Effectiveness","A Phase 1\u002F2 Trial Evaluating the Combination of Temozolomide and the Ataxia Telangiectasia and Rad3-Related Inhibitor M1774","Inclusion Criteria:\n\n* Patients must have histologically or cytologically confirmed diagnosis of metastatic advanced cancer.\n* In dose escalation, any solid tumor patients with either O6-methylguanine DNA methyltransferase (MGMT) promoter hypermethylation positivity on testing \u002F pre-screening of archival tissue OR an extracranial solid tumor where TMZ is considered a standard of care per National Comprehensive Cancer Network (NCCN) guidelines (neuroendocrine tumor, small cell lung cancer, melanoma or soft tissue sarcoma). The tumor lesion must be safely accessible to a mandatory biopsy. Patients with MGMT promoter hypermethylated colorectal cancer must be mismatch repair proficient \u002F microsatellite stable.\n* In phase 2, only patients with mismatch repair proficient \u002F microsatellite stable colorectal cancer that have MGMT promoter hypermethylation positivity on pre-screening of archival tissue will be eligible.\n* In dose escalation, patients must have progressed after treatment with all available therapies including immunotherapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment. Patients may not have previously received temozolomide or an ataxia telangiectasia and rad3-related (ATR) inhibitor.\n* For patients with mismatch repair proficient \u002F microsatellite stable colorectal cancer in the phase 2 portion, patients must have received prior therapy with 1 or more systemic therapies in the metastatic setting that includes 5-fluorouracil, irinotecan, and oxaliplatin. Patients with microsatellite stable colorectal cancer (mCRC) need to have had exposure, unless contraindicated, to all 3 of oxaliplatin, irinotecan, and fluoropyrimidine (FP).\n\nThe use of 5-fluorouracil and oxaliplatin in the adjuvant setting is acceptable, provided the development of metastatic disease was less than 6 months after the completion of adjuvant therapy.\n\nPatients with a prior hypersensitivity reaction to oxaliplatin in the adjuvant setting do not require retreatment in the metastatic setting.\n\n* Age \\>=18 years. Because no dosing or adverse event data are currently available on the use of M1774 in combination with temozolomide in patients \\\u003C 18 years of age, children are excluded from this study.\n* Measurable disease on CT and\u002For MRI per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria.\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2 (or Karnofsky \\>= 60%).\n* Hemoglobin \\>=10 g\u002FdL (No blood transfusions are allowed within 14 days of cycle 1 day 1 \\[C1D1\\]).\n* White blood cells (WBC) \\> 3 x 10\\^9\u002FL.\n* Absolute neutrophil count \\>= 1,500\u002FmcL.\n* Platelets \\>= 100,000\u002FmcL.\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN).\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine-aminotransferase (ALT) (serum glutamic-pyruvic transaminase \\[SGPT\\]) =\\\u003C 3 x institutional ULN except for when liver metastases are present, in which case they must be =\\\u003C 5 x institutional ULN.\n* Glomerular filtration rate (GFR) \\>= 60 mL\u002Fmin\u002F1.73 m\\^2.\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months 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 treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for 4 weeks.\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 are eligible for this trial.\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* The effects of M1774 on the developing human fetus are unknown. For this reason and because ATR inhibitors agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 6 months after completion of M1774 administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of M1774 administration.\n* Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia and neuropathy, which may be =\\\u003C grade 2.\n* History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to M1774 or temozolomide, including dacarbazine.\n* Patients with uncontrolled intercurrent illness.\n* Pregnant women are excluded from this study because M1774 is an ATR inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M1774 breastfeeding should be discontinued if the mother is treated with M1774. These potential risks also apply to temozolomide.\n* Patients with a prior history of ataxia telangiectasia.\n* Patients who are not able to swallow orally administered medication or have gastrointestinal disorders likely to interfere with absorption of the study medication.\n* Patients who cannot discontinue proton-pump inhibitors (PPIs) while taking M1774. H-2 receptor antagonists are allowed but should not be taken within 12 hours before or 2 hours after M1774. Antacids are also allowed, but should not be taken 2 hours before 2 hours after M1774.\n* Extensive RT involving greater than 30% of the bone marrow is not permitted during the study.\n* A Fridericia's correction formula (QTcF) \\> 480 ms is exclusionary given the potential for QT.","ALL","18 Years",{"count":19,"type":20},42,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE1","PHASE2","This phase I\u002FII trial studies the side effects and best dose of temozolomide and M1774 and how well they works in treating patients with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and may have spread to nearby tissue, lymph nodes, or distant parts of the body (advanced). Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. M1774 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Adding M1774 to temozolomide may shrink or stabilize cancer for longer than temozolomide alone.",[27,28,29,30,31,32,33],"Advanced Malignant Solid Neoplasm","Advanced Microsatellite Stable Colorectal Carcinoma","Hematopoietic and Lymphatic System Neoplasm","Metastatic Malignant Solid Neoplasm","Metastatic Microsatellite Stable Colorectal Carcinoma","Stage III Colorectal Cancer AJCC v8","Stage IV Colorectal Cancer AJCC v8","RECRUITING","2026-06-13",{"date":37,"type":38},"2026-06-16","ACTUAL",{"date":40,"type":38},"2023-09-28",{"date":42,"type":20},"2027-03-01",{"name":44,"class":45},"National Cancer Institute (NCI)","NIH",23,{"id":48,"slug":49,"hasResults":11,"nctId":50,"briefTitle":51,"officialTitle":52,"acronym":4,"eligibilityCriteria":53,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":54,"targetDuration":4,"studyType":21,"phases":56,"briefSummary":57,"conditions":58,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":60,"lastUpdatePostDateStruct":61,"startDateStruct":63,"completionDateStruct":65,"leadSponsor":67,"locationsCount":68},"100566350","phase-1-testing-the-addition-of-an-anti-cancer-drug-abemaciclib-to-the-usual-chemotherapy-treatment-5-fluorouracil-for-metastatic-refractory-colorectal-cancer-100566350","NCT06654037","Testing the Addition of an Anti-Cancer Drug, Abemaciclib, to the Usual Chemotherapy Treatment (5-Fluorouracil) for Metastatic, Refractory Colorectal Cancer","A Phase 1 Study of 5-Fluorouracil in Combination With Abemaciclib in Metastatic, Refractory CRC","Inclusion Criteria:\n\n* Patients must have histologically or cytologically confirmed microsatellite stability (MSS) metastatic colorectal cancer where patients have progressed on standard therapies which would have included 5-FU or capecitabine, oxaliplatin, and irinotecan. Patients must have had progression of disease (PD) or intolerance to bevacizumab and anti-EGFR antibodies (cetuximab or panitumumab) in patients who have left-sided and RAS-wildtype CRC\n* Patients must have measurable disease\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of abemaciclib in combination with 5-FU in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)\n* Hemoglobin ≥ 8 g\u002FdL\n* Absolute neutrophil count ≥ 1,500\u002FmcL\n* Platelets ≥ 100,000\u002FmcL\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002F alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 x institutional ULN for patients who do not have liver metastases, and ≤ 5 x institutional ULN for patients with liver metastases\n* Glomerular filtration rate (GFR) ≥ 50 mL\u002Fmin\u002F1.73 m\\^2\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months 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 treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\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 are eligible for this trial\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 II or better\n* Patients must have available archival tumor tissue at the time of patient enrollment for molecular profiling studies. A biopsy may be done if archival tissue is not available\n* Palliative radiation for symptom management to a metastatic site will be permitted during the course of the study. Please discuss specific cases with the national principal investigator (PI)\n* Patients must have completed previous systemic therapy for at least five half-lives or 2 weeks, whichever is shorter, prior to study dosing\n* Patients who have not had major surgery within 14 days prior to randomization\n* Patients who do not have serious and\u002For uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \\[e.g. estimated creatinine clearance \\\u003C 30ml\u002Fmin\\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea)\n* Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization\n* Patients who are able to swallow oral medications\n* Patients who do not have a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest\n* Patients who do not have an active systemic bacterial infection (requiring intravenous \\[IV\\] antibiotics at time of initiating study treatment) or fungal infection\n* The effects of abemaciclib on the developing human fetus are unknown. For this reason and because cyclin-dependent kinases (CDK) inhibiting agents as well as other therapeutic agents used in this trial are known to be teratogenic, men and women treated or enrolled on this protocol must also agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to the study, for the duration of study participation, and 3 months after completion of abemaciclib and fluorouracil. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\n\nExclusion Criteria:\n\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia or grade 2 peripheral neuropathy. Patients who are experiencing immune related adverse events (AEs) which are adequately treated with hormone replacement therapy, including diabetes on insulin regimen, hypothyroidism on levothyroxine, and adrenal insufficiency on steroid replacement will also be eligible\n* Patients who are receiving any other investigational agents. There is to be a washout period of two weeks or five half-lives, whichever is shorter, for all investigational agents prior to treatment initiation on this study. Individual cases can be discussed with the national PI\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib or other agents (5-FU) used in study such as a previous intolerance to 5-FU or capecitabine, including patients with known or suspected dihydropyrimidine dehydrogenase deficiency\n* Patients who have received previous treatment with a CDK4\u002F6 inhibitor\n* Patients with a gastrointestinal pathology or history that adversely impacts the ability to take or absorb oral medication\n* Patients with peritoneal metastases complicated by ascites which are refractory to diuretic therapy and requires therapeutic paracenteses more than once every 2 weeks\n* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A enzymes before enrollment or while on protocol therapy are ineligible. Patients receiving moderate CYP3A inhibitors or inducers will be monitored. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous\n* Pregnant women are excluded from this study because abemaciclib is a CDK-inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with abemaciclib, breastfeeding should be discontinued if the mother is treated with abemaciclib. These potential risks may also apply to other agents used in this study",{"count":55,"type":20},39,[23],"This phase I trial tests the safety, side effects, and best dose of abemaciclib in combination with 5-fluorouracil and how well it works in treating patients with colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that has not responded to treatment (refractory). Abemaciclib, a type of cyclin-dependent kinase inhibitor, blocks certain proteins, which may help keep tumor cells from growing. 5-fluorouracil, a type of antimetabolite, stops cells from making deoxyribonucleic acid (DNA) and may kill tumor cells. Giving abemaciclib in combination with 5-fluorouracil may be safe, tolerable, and\u002For effective in treating patients with metastatic and refractory colorectal cancer.",[31,59,33],"Refractory Microsatellite Stable Colorectal Carcinoma","2026-05-12",{"date":62,"type":38},"2026-05-13",{"date":64,"type":38},"2025-04-18",{"date":66,"type":20},"2027-04-01",{"name":44,"class":45},8,{"id":70,"slug":71,"hasResults":11,"nctId":72,"briefTitle":73,"officialTitle":74,"acronym":4,"eligibilityCriteria":75,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":76,"targetDuration":4,"studyType":21,"phases":78,"briefSummary":79,"conditions":80,"keywords":81,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":87,"lastUpdatePostDateStruct":88,"startDateStruct":90,"completionDateStruct":92,"leadSponsor":94,"locationsCount":97},"100614601","phase-1-combination-immunotherapy-for-the-treatment-of-chemotherapy-refractory-metastatic-mss-crc-100614601","NCT07281716","Combination Immunotherapy for the Treatment of Chemotherapy-refractory Metastatic MSS CRC","A Phase 1b\u002F2 Study of Combination Immunotherapy for the Treatment of Chemotherapy-refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer (CRC)","Inclusion Criteria:\n\n* Patients must have a pathologically confirmed diagnosis of non-MSI-H\u002FpMMR CRC.\n* Patients must have progressed (clinically or radiographically) on or after standard chemotherapy, including fluoropyrimidines, oxaliplatin, and irinotecan, or are intolerant to standard chemotherapy. Patients may have received, if eligible, anti-VEGF or anti-EGFR antibodies in combination with chemotherapy.\n* Patients must have at least 1 measurable target lesion at baseline ≥ 10mm in the longest diameter.\n* Patient must be willing and able to provide blood samples (6 heparinized, and two streck tubes, roughly 70 - 80 mL) at the time points indicated in the Study Calendar.\n* Patients must have at least 1 lesion suitable for core needle biopsies.\n* Patients must be willing and able to have core needle biopsies, if clinically feasible (Goal 3-6 biopsies, final number to be determined by the interventionalist performing the procedure as safe), of tumor prior to initiation of study drug. Should patients undergo pre-treatment or on-treatment biopsy procedure and inadequate number of biopsies are obtained, they may proceed with initiation\u002Fcontinuation of treatment at the discretion of the investigator and treating physician.\n* Age ≥ 18 years.\n* ECOG Performance Status 0-1 (Karnofsky ≥60%, see https:\u002F\u002Fecog-acrin.org\u002Fresources\u002Fecog-performance-status\u002F). o Patients with performance status \\>1 carrying long-term disability (such as cerebral palsy) where the disability is not acute nor progressive, and unlikely to significantly affect their response to therapy may be enrolled at the investigator's discretion\n* Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 4 months following completion of therapy. Should a study participant become pregnant or suspect pregnancy while participating in this study, the study participant should inform the treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: o Has not undergone a hysterectomy or bilateral oophorectomy; or o Has not been naturally postmenopausal for at least 12 consecutive months\n* Ability to understand and the willingness to sign a written informed consent. • Adequate organ and marrow function\n\nExclusion Criteria:\n\n* Patients who have had chemotherapy within 14 days from start of therapy.\n* Palliative radiotherapy is permitted at anytime, if deemed in the best interest of the patient.\n* Patients may not be receiving any other investigational agents.\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (≤10days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Patients who have undergone major surgery within 4 weeks prior to the first dose of treatment.\n* Patients who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.\n* Patients who discontinued prior immune checkpoint inhibitors due to immune-related adverse events are not eligible for enrollment.\n* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.\n* Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable.\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.\n* HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with \\\u003C200 CD4+ T cells\u002Fmicroliter in the peripheral blood. HIV testing is mandatory for patients with no known history of HIV. For such patients HIV testing will be considered SOC.\n* Has known active Hepatitis B (e.g., HBV detected by PCR or active Hepatitis C (e.g., HCV RNA \\[qualitative\\] is detected). Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.\n* History of allogeneic hematopoietic cell transplantation or solid organ transplantation.\n* Receipt of a live vaccine within 28 days of planned start of study medication.\n* Receipt of etanercept or other TNF-α inhibitors within 28 days of planned start of the study medication.\n* Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps).\n* Principal investigator believes that for one or multiple reasons the patient will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the patient.\n* History of irAE in response to prior immunotherapy that has not improved to a Grade 0 or 1; this does not include chronic conditions such as endocrinopathies which can be treated with hormone replacement therapy.\n* History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis attributed to prior use of cancer immunotherapy that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted.",{"count":77,"type":20},24,[23,24],"Phase 1b\u002F2 open-label study evaluates the safety, tolerability, and efficacy of combination immunotherapy with nadunolimab (anti-IL-1RAP) and toripalimab (anti-PD-1) in patients with chemotherapy-refractory metastatic microsatellite stable (MSS) colorectal cancer. Phase 1b will assess dose-limiting toxicity (DLT), while Phase 2 will evaluate objective response rate (ORR), including progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response (DOR). Exploratory analyses will investigate immunomodulatory effects through tumor and peripheral blood studies, and treatment will continue every 3 weeks for up to 1 year or until disease progression.",[31],[82,83,84,85,86],"Colorectal Cancer(CRC)","Chemotherapy-refractory colorectal cancer","Microsatellite stable colorectal cancer (MSS CRC)","Metastatic colorectal cancer","Chemotherapy-resistant CRC","2026-02-17",{"date":89,"type":38},"2026-02-19",{"date":91,"type":38},"2025-12-01",{"date":93,"type":20},"2028-12-15",{"name":95,"class":96},"Dan Feng","OTHER",1,{"id":99,"slug":100,"hasResults":11,"nctId":101,"briefTitle":102,"officialTitle":103,"acronym":4,"eligibilityCriteria":104,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":105,"targetDuration":4,"studyType":21,"phases":107,"briefSummary":108,"conditions":109,"keywords":4,"overallStatus":110,"whyStopped":4,"lastUpdateSubmitDate":111,"lastUpdatePostDateStruct":112,"startDateStruct":114,"completionDateStruct":116,"leadSponsor":118,"locationsCount":97},"100620883","phase-1-ivonescimab-and-adg126-alone-and-in-combination-with-leucovorin-and-fluorouracil-or-folfiri-regimen-for-the-treatment-of-microsatellite-stable-advancedmetastatic-colorectal-cancer-100620883","NCT07363408","Ivonescimab and ADG126, Alone, and in Combination With Leucovorin and Fluorouracil or FOLFIRI Regimen for the Treatment of Microsatellite Stable Advanced\u002FMetastatic Colorectal Cancer","A Phase I Clinical Trial of Ivonescimab and ADG126, Alone, and in Combination With 5-FU\u002FLV or FOLFIRI in MSS Advanced\u002FMetastatic Colorectal Cancer","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n* Agreement to blood collection for correlative analysis at baseline, 4 weeks, and 8 weeks, and then every subsequent 8 weeks\n* Age: ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) ≤ 1\n* Histologically confirmed advanced\u002Fmetastatic MSS colorectal cancer. MSS status must have been confirmed by a Clinical Laboratory Improvement Amendments (CLIA) certified assay\n* Measurable disease by RECIST 1.1\n* Fully recovered from the acute, clinically significant, toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy\n* ARM A ONLY: Patients should not have evidence of hepatic metastatic disease\n* ARM A ONLY: Patients should have progressed following irinotecan, oxaliplatin, fluoropyrimidine, and an anti-EGFR if clinically indicated\n* ARM B ONLY: Patient is eligible for maintenance 5-FU\u002FLV or 5-FU\u002FLV bevacizumab\n* ARM B ONLY: No history of significant toxicity to 5-FU\u002FLV that required dose reduction in infusional 5-FU dosing\n* ARM C ONLY: Patient is eligible for FOLFIRI chemotherapy\n* ARM C ONLY: No history of significant toxicity to 5-FU\u002FLV or irinotecan that required dose reduction in infusional 5-FU dosing or irinotecan\n* ARM C ONLY: No prior progression on prior irinotecan and no prior dose reduction on irinotecan due to toxicity\n* Absolute neutrophil count (ANC) ≥ 1.5 × 10\\^9\u002FL\n\n  * NOTE: no blood transfusions or growth factor therapy used within 7 days of the screening complete blood count (CBC)\n* Platelets ≥ 100 × 10\\^9\u002FL\n\n  * NOTE: no blood transfusions or growth factor therapy used within 7 days of the screening CBC\n* Hemoglobin ≥ 9.0 g\u002FdL\n\n  * NOTE: no blood transfusions or growth factor therapy used within 7 days of the screening CBC\n* Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); For patients with liver metastases or confirmed\u002Fsuspected Gilbert syndrome, TBIL ≤ 3 × ULN\n* Aspartate aminotransferase (AST) ≤ 2.5 x ULN; For patients with liver metastases ≤ 5 x ULN\n* Alanine aminotransferase (ALT) ≤ 2.5 x ULN; For patients with liver metastases ≤ 5 x ULN\n* Creatinine clearance of ≥ 50 mL\u002Fmin per 24 hour urine test or the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) value ≥ 30 mL\u002Fmin using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (adjustment by body surface area \\[BSA\\] is not required for eGFR; eGFR can be determined using the calculator from the National Kidney Foundation website \\[www.kidney.org\\])\n* International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN (unless abnormalities are unrelated to coagulopathy). This applies only to patients who are not on therapeutic anti-coagulation. Patients receiving therapeutic anti-coagulation should be on a stable dose\n* Urine protein \\\u003C 2+ or 24-hour urine protein quantification \\\u003C 1.0 g\n* For patients with KNOWN history of HIV, hepatitis C virus (HCV) and\u002For hepatitis B virus (HBV) seropositivity only, nucleic acid quantitation for their virus must be performed.\n\n  * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load and a cd4 \\> 400 are eligible for this trial.\n  * Patients with known active hepatitis B are required to have hepatitis B DNA \\\u003C 200 IU\u002Fml by polymerase chain reaction (PCR) and on appropriate anti-viral therapy with acceptable tolerability for one month prior to randomization.\n  * All patients with known active hepatitis C (hepatitis C virus \\[HCV\\] antibody positive with HCV RNA levels above the lower limit of detection) are excluded\n* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test\n\n  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n* Female patient 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 6 months after the last dose of study drug. 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 6 months after the last dose of study drug. 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 6 months after the last dose of study drug\n\n  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \\> 1 year (women only)\n\nExclusion Criteria:\n\n* Major surgical procedures or serious trauma within 4 weeks prior to study entry, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to study entry\n* Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation\n* Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days or five half-lives (whichever is shorter for non-radiation therapy) prior to day 1 of protocol therapy\n* Strong CYP3A4 inducers\u002F inhibitors within 14 days prior to day 1 of protocol therapy (Arm C only)\n* UGT1A1 inhibitors within 14 days prior to day 1 of protocol therapy (Arm C only)\n* Any other anti-cancer therapy is prohibited, including but not limited to antibody-based therapy, retinoids, nitrosourea therapy, mitomycin C, small molecule tyrosine kinase inhibitors, proprietary Chinese medicines with anti-cancer activity, or radiotherapy\n* Herbal medications must be cleared by the principal investigator (PI)\n* Prior exposure to PD-1 or PD-L1 or CTLA-4 targeting agents\n* History of bleeding tendencies or coagulopathy and\u002For clinically significant bleeding symptoms or risk within 4 weeks prior to study entry, including but not limited to:\n\n  * Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots) Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed\n  * Nasal bleeding\u002Fepistaxis (bloody nasal discharge is allowed)\n  * Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to study entry is not allowed. The use of full-dose anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution or with the use of factor Xa inhibitors\n* Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy\n* Active autoimmune or lung disease requiring systemic therapy (eg, with disease modifying drugs, prednisone \\> 10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to study entry, however the following will be allowed:\n\n  * Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.\n  * Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted\n* History of major diseases before study entry, specifically:\n\n  * Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \\[NYHA\\] classification ≥ grade 2) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease) that required hospitalization within 12 months prior to study entry, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)\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 study entry\n  * History of any grade arterial thromboembolic event, grade 3 and above venous thromboembolic event, as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to study entry\n  * Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before study entry\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 study entry\n* Imaging during the screening period shows that the patient has:\n\n  * Radiologically documented evidence of major blood vessel invasion or fistula\n* Symptomatic central nervous system (CNS) metastases, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to study entry, potential need for CNS radiation within the first cycle, or leptomeningeal disease. Note: Patients must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent)\n* Live vaccine or live attenuated vaccine within 4 weeks prior to planned study entry, or if scheduled to receive a live vaccine or live attenuated vaccine during the study period. Inactivated vaccines are permitted\n* Severe infection within 4 weeks prior to study entry, 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 study entry, (excluding antiviral therapy for hepatitis B or C)\n* Has pre-existing peripheral neuropathy that is ≥ grade 2 by CTCAE version 5.0\n* Uncontrolled pleural effusions, pericardial effusions, or ascites that is clinically symptomatic or required paracentesis in the last 4 weeks prior to enrollment\n* History of non-infectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease\n* Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)\n* Current use of systemic corticosteroids (\\>10 mg daily prednisone or equivalent)\n* High risk for bowel perforation such as obstructive gastrointestinal (GI) findings on imaging or symptoms suggesting bowel obstruction (post-prandial cramping, nausea, or vomiting)\n* Presence of an enteric stent\n* Open non-healing wounds\n* History of bowel perforation unless related to the primary tumor and unless the tumor was resected or the patient has been diverted proximal to the tumor\n* Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies; history of allergic reactions attributed to compounds of similar chemical or biologic composition to any study agent\n* History or current evidence of any condition (medical \\[including adverse events from prior anticancer therapy, disorders secondary to tumor\\], surgical or psychiatric \\[including substance abuse\\]), or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, might lead to higher medical risk and\u002For is not in the best interest of the patient to participate, in the opinion of the treating investigator\n* Clinically significant uncontrolled illness\n* Other active malignancy. 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 are eligible for this trial\n* Patient is breastfeeding or plans to breastfeed during the study\n* Females only: Pregnant\n* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics)",{"count":106,"type":20},30,[23],"This phase I trial studies the safety, side effects, and best dose of ADG126, in combination with ivonescimab alone, in combination with ivonescimab, leucovorin, and fluorouracil, or in combination with ivonescimab and leucovorin, fluorouracil, and irinotecan (FOLFIRI regimen) in treating patients with microsatellite stable (MSS) colorectal cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as ivonescimab and ADG126, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ivonescimab may also stop or slow the cancer by blocking the growth of new blood vessels necessary for tumor growth. Leucovorin calcium is a type of drug called a folic acid analog, which means it is similar to the vitamin folic acid. It is used in combination with certain chemotherapy drugs to enhance their ability to kill tumor cells or to lessen their harmful side effects. Fluorouracil is a type of chemotherapy called an antimetabolite, which is a drug that mimics a natural chemical and prevents its use in cells. It interferes with the production of a key component of deoxyribonucleic acid (DNA), which prevents the DNA from copying itself. This causes tumor cells and other rapidly dividing cells to die. Fluorouracil also gets incorporated into ribonucleic acid (RNA) and DNA, disrupting critical cell functions. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Giving ADG126 with ivonescimab, with or without leucovorin and fluorouracil or FOLFIRI regimen, may be safe in treating patients with MSS advanced\u002Fmetastatic colorectal cancer.",[28,31,32,33],"NOT_YET_RECRUITING","2026-01-22",{"date":113,"type":38},"2026-01-23",{"date":115,"type":20},"2026-07-21",{"date":117,"type":20},"2027-07-21",{"name":119,"class":96},"City of Hope Medical Center"]