[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-colorectal-cancer\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-colorectal-cancer":28},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,91,0,25,[9,49,74,103,133,162,174,196,220,248,296,320,339,367,398,417,435,447,471,507,533,551,576,603,617],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":29,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":38,"startDateStruct":41,"completionDateStruct":43,"leadSponsor":45,"locationsCount":48},"100053467","phase-1-phase-iii-study-of-the-combination-immunotherapy-regimen-sx-682-triadeno-vaccine-retifanlimab-and-il-15-agonist-n-803-star15-for-metastatic-colorectal-cancer-mcrc-100053467",false,"NCT06149481","Phase I\u002FII Study of the Combination Immunotherapy Regimen: SX-682, TriAdeno Vaccine, Retifanlimab and IL-15 Agonist N-803 (STAR15) for Metastatic Colorectal Cancer (mCRC)","* INCLUSION CRITERIA:\n* Participants with histologically confirmed colorectal cancer and evidence of metastatic disease.\n* Participants must have received, been ineligible to receive, or refused to receive two lines of standard systemic therapy i.e., a fluoropyrimidine with oxaliplatin or irinotecan with bevacizumab, regorafenib, trifluridine, and (if history of RAS wild-type) EGFR-targeted therapy. Participants must have received one line of systemic checkpoint inhibitor if history of advanced microsatellite instability-high \\[MSI-H\u002FdMMR\\]) metastatic colon cancer.\n* Participants who had progressive disease within 6 months before study treatment following standard adjuvant therapy are eligible if they have not received systemic therapy for metastatic disease. Participants with a history of MSI-H\u002FdMMR must have also received one line of checkpoint inhibitor therapy.\n* Age \\>= 18 years.\n* Measurable disease per RECIST 1.1.\n* ECOG performance status \\\u003C= 2.\n* Adequate organ and marrow as a function defined below:\n\n  * absolute neutrophil count (ANC) \\>= 1,500 cells\u002Fmm\\^3\n  * platelet count \\>= 100,000 cells\u002Fmm\\^3\n  * hemoglobin (Hgb) \\>= 9 g\u002FdL\n  * total bilirubin level \\\u003C 1.5 x upper limit of normal (ULN)\n  * alanine aminotransferase (ALT) \\\u003C= 2.5 x ULN OR \\\u003C= 5 x ULN for participants with liver metastases\n  * aspartate aminotransferase (AST) level \\\u003C= 2.5 x ULN OR \\\u003C= 5 x ULN for participants with liver metastases\n  * creatinine clearance (CrCl) calculated by Cockroft-Gault formula \\>= 50 mL\u002Fmin\n* Resolution of toxic effect(s) of prior anti-cancer therapy (except alopecia and neuropathy) to Grade \\\u003C=1 or to \\\u003C=2 if effective medical management of those toxicities is in place such that they are controlled per standard of care (e.g., grade 2 hypothyroidism requiring oral thyroid replacement).\n* Participants with treated brain metastases are eligible if clinically appropriate follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.\n* Participants positive for human immunodeficiency virus (HIV) are eligible if they are compliant with appropriate anti-retroviral therapy for at least 6 months, have HIV viral load \\\u003C400 copies\u002FmL, and a CD4 count \\> 350 cells\u002Fmicroliter at screening.\n* Participants positive for Hepatitis C virus (HCV) are eligible if they have completed definitive anti-viral therapy and have an undetectable viral load.\n* Individuals of child-bearing potential (IOCBP) and individuals who can father children must agree to use an effective method of contraception (barrier, hormonal, intrauterine device \\[IUD\\], surgical sterilization) at study entry and up to 6 months after the last dose of the study drug(s).\n* Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 6 months after study treatment discontinuation.\n* Participants must have lesion(s) accessible for biopsy (other than used for measurement of disease) and be willing to undergo mandatory study biopsies in the phase 1 portion of the study. Lesions to be biopsied will be determined safely accessible by the provider performing the biopsy (e.g. interventional radiology if a liver or lung biopsy) prior to performing the biopsy. Note: If Phase 2 opens, per the investigator s discretion, if biopsy is strenuous to obtain, e.g., no easily accessible lesions are available or the subject\n\ncondition is not amenable for biopsy, then the subject will be eligible for enrollment without biopsy at screening and for continuation of treatment without on-treatment study biopsy.\n\n-Participants must be able to understand and willing to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* Participants with prior investigational drug, chemotherapy, immunotherapy, or any prior therapeutic radiotherapy within 14 days prior to study treatment initiation.\n* Participants with palliative radiotherapy performed within 7 days prior to study treatment initiation.\n* Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\\> 10 mg\u002Fday of prednisone or equivalent) with the exception of:\n\n  * intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections in participants with asthma\n  * using topical, ocular, intra-articular, or intranasal corticosteroids (with minimal systemic absorption\n  * brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy).\n* Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis. Participants with chronic post-radiation pulmonary changes\u002Fscarring that is asymptomatic are eligible.\n* Active infections requiring systemic antibiotics or antifungal or antiviral treatment within 8 days prior to treatment initiation. Participants who have had appropriate antibiotics initiated but are still completing the treatment course are eligible if clinically improved or had minimal symptoms at presentation (e.g., urinary tract infection or pharyngeal streptococcal infection without evidence of systemic inflammatory response).\n\n  * History of organ transplant, including allogeneic stem cell transplantation.\n  * Participants who experienced immune-related toxicity during prior checkpoint inhibitor therapy for which permanent discontinuation of therapy was recommended (per product label or consensus guidelines) or any immune-related toxicity requiring systemic corticosteroids (with the exception of endocrinopathy that is well controlled on replacement hormones).\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs.\n* Receipt of a live vaccine within 28 days prior to treatment initiation. Note: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster (chickenpox), yellow fever, rabies, 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* History of infection with Hepatitis B virus (HBV) unless on suppressive therapy. Individuals with serologic evidence of a resolved prior HBV infection (i.e., HBsAgnegative and anti-HBc positive) are eligible.\n* Pregnancy confirmed with Beta-human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test performed in IOCBP at screening.\n* Uncontrolled intercurrent illness that would limit compliance with study requirements.","ALL","18 Years","120 Years",{"count":20,"type":21},60,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE1","PHASE2","Background:\n\nEach year, more than 32,000 people in the United States are diagnosed with colorectal cancer that has returned or progressed after treatment and spread to other organs. This is called metastatic colorectal cancer (mCRC). Most people with mCRC survive only about 2 years.\n\nObjective:\n\nTo test the ability of a combination of up to 4 experimental anti-cancer drugs treat mCRC. The names of these drugs are retifanlimab, TriAdeno vaccine, N-803, and SX-682. They are described below.\n\nEligibility:\n\nAdults aged 18 years or older with mCRC. Participants must have\n\nDesign:\n\nParticipants will be screened. This includes having a physical exam, blood tests, urine tests, and imaging tests. If signed on to the study, participants will have 2 tumor biopsies. One when starting the study and once about 8 weeks after bring on the study. Participants will receive $500 for each biopsy.\n\nParticipants will be treated with either 3 or 4 drugs and will receive a detailed calendar explaining when each drug is given.\n\nRetifanlimab is given every 4 weeks through an IV (an IV is tube attached to a needle inserted into a vein in the arm). N-803 is injected under the skin on the abdomen every 4 weeks.\n\nTriAdeno vaccine is injected under the skin of the upper arm or thigh once a month for 3 doses and then once every 3 months.\n\nSome participants will also receive a 4th drug. SX-682 is a pill taken by mouth. Participants will take this drug 2 times a day at home for about 3 weeks of each month.\n\nStudy treatment will continue up to 2 years. Follow-up phone calls\u002Femails may continue for 3 more years.",[28],"Metastatic Colorectal Cancer",[30,31,32,33,34,35],"Monoclonal Antibody","Brachyury","MUC-1","Immunoglobulin G cytokine fusion protein","chemokine antagonist","Small Molecule","RECRUITING","2026-07-10",{"date":39,"type":40},"2026-07-13","ACTUAL",{"date":42,"type":40},"2024-03-26",{"date":44,"type":21},"2030-10-31",{"name":46,"class":47},"National Cancer Institute (NCI)","NIH",1,{"id":50,"slug":51,"hasResults":12,"nctId":52,"briefTitle":53,"officialTitle":54,"acronym":55,"eligibilityCriteria":56,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":57,"targetDuration":4,"studyType":22,"phases":59,"briefSummary":60,"conditions":61,"keywords":62,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":65,"startDateStruct":66,"completionDateStruct":68,"leadSponsor":70,"locationsCount":73},"100053954","phase-2-a-study-to-evaluate-the-adverse-events-and-efficacy-of-intravenous-iv-of-telisotuzumab-adizutecan-in-combination-with-iv-oxaliplatin-fluorouracil-folinic-acidleucovorin-bevacizumab-panitumumab-in-adult-participants-with-metastatic-colorectal-cancer-100053954","NCT06820463","A Study to Evaluate the Adverse Events, and Efficacy of Intravenous (IV) of Telisotuzumab Adizutecan in Combination With IV Oxaliplatin, Fluorouracil, Folinic Acid\u002FLeucovorin, Bevacizumab, Panitumumab in Adult Participants With Metastatic Colorectal Cancer","A Phase 2, Open-Label, Randomized, Master Protocol Study to Evaluate Safety and Efficacy of Multiple Treatment Combinations With Telisotuzumab Adizutecan in Subjects With Metastatic Colorectal Cancer","AndroMETa-CRC","Inclusion Criteria:\n\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n* Laboratory values meeting the criteria within the protocol.\n* Has measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1.\n\nExclusion Criteria:\n\n* Prior systemic regimen containing c-Met targeting agent(s) (e.g., antibody, antibody drug conjugate, bispecific) and\u002For any topoisomerase inhibitor(s) (e.g., irinotecan).\n* History of other malignancies within 5 years prior to screening, except for malignancies with a negligible risk of metastasis or death.",{"count":58,"type":21},390,[25],"CRC is the third most common type of cancer diagnosed worldwide with developed countries at highest risk. The purpose of this study is to assess adverse events and change in disease activity when telisotuzumab adizutecan is given in combination with oxaliplatin, fluorouracil (5FU), leucovorin (LV) (FOLFOX), and bevacizumab or panitumumab.\n\nTelisotuzumab adizutecan is an investigational drug being developed for the treatment of mCRC. Fluorouracil and leucovorin are drugs approved for the treatment of mCRC. This study will be divided into two stages, with the first stage treating participants with increasing doses of telisotuzumab adizutecan with FOLFOX and bevacizumab or 5FU\u002FLV and panitumumab until the dose reached is tolerable and expected to be efficacious. Participants will then be randomized into 3 groups called treatment arms where one group will receive one of two optimized doses of telisotuzumab adizutecan from the dose escalation phase with FOLFOX and bevacizumab or 5FU\u002FLV and panitumumab, or a comparator of FOLFOX and bevacizumab or panitumumab. Approximately 390 adult participants with mCRC will be enrolled in the study in 100 sites worldwide.\n\nIn the dose escalation stage participants will be treated with increasing intravenous (IV) doses of telisotuzumab adizutecan with FOLFOX and bevacizumab or 5FU\u002FLV and panitumumab until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage participants will be receive FOLFOX or receive 5FU\u002FLV, but with one of two optimized doses of telisotuzumab adizutecan, or a comparator of FOLFOX and bevacizumab\u002Fpantitumumab. The study will run for a duration of approximately 6 years.\n\nThere may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.",[28],[28,63,64],"AndroMETa-CRC-533","Telisotuzumab Adizutecan",{"date":39,"type":40},{"date":67,"type":40},"2025-04-24",{"date":69,"type":21},"2028-04",{"name":71,"class":72},"AbbVie","INDUSTRY",56,{"id":75,"slug":76,"hasResults":12,"nctId":77,"briefTitle":78,"officialTitle":79,"acronym":80,"eligibilityCriteria":81,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":82,"enrollmentInfo":83,"targetDuration":4,"studyType":22,"phases":85,"briefSummary":86,"conditions":87,"keywords":88,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":95,"startDateStruct":96,"completionDateStruct":98,"leadSponsor":100,"locationsCount":102},"100054276","phase-2-a-study-of-novel-study-interventions-and-combinations-in-participants-with-colorectal-cancer-100054276","NCT06792695","A Study of Novel Study Interventions and Combinations in Participants With Colorectal Cancer","A Phase II, Open-label, Multicenter, Master Protocol to Evaluate the Safety and Efficacy of Novel Study Interventions and Combinations in Participants With Colorectal Cancer (CANTOR)","CANTOR","Overall Inclusion Criteria:\n\n* Histopathologically confirmed colorectal adenocarcinoma.\n* Provision of FFPE tumor sample collected as per SoC.\n* Presence of measurable disease by RECIST 1.1 criteria.\n* ECOG performance status of 0 or 1.\n* Life expectancy ≥ 12 weeks at the time of screening.\n\nSubstudy Inclusion Criteria:\n\n* No radiological evidence of liver metastasis.\n* No prior systemic therapy for mCRC, except for neoadjuvant\u002Fadjuvant chemotherapy where, \\> 6 months have elapsed between completion of therapy and documented date of diagnosis of recurrent or metastatic disease.\n* Known pMMR\u002FMSS status (only pMMR\u002FMSS mCRC allowed).\n* Adequate organ and bone marrow function\n* Body weight \\> 35 kg at screening and at randomization.\n* Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.\n\nOverall Exclusion Criteria:\n\n* Central nervous system metastases or spinal cord compression\n* Known history of severe allergy to any monoclonal antibody or study intervention.\n* Any unresolved toxicity CTCAE Grade ≥ 2 from a previous anticancer therapy.\n* History of another primary malignancy.\n\nSubstudy Exclusion Criteria:\n\n* Potentially resectable disease with multidisciplinary plan for radical surgery.\n* Active or prior documented autoimmune or inflammatory disorders or cardiac conditions.\n* Participants with a prior history of hypertensive crisis or hypertensive encephalopathy or bleeding risks.\n* Deep venous thrombosis, pulmonary embolism, arterial thrombosis, transient ischemic attack or cerebrovascular accident.\n* History of abdominal or tracheoesophageal fistula, GI perforation and\u002For fistulae, or intraabdominal abscess within 6 months prior to randomization.\n* Prior exposure to immune mediated therapy.","130 Years",{"count":84,"type":21},80,[25],"The main purpose of this study is to evaluate the safety and efficacy of novel study interventions and combinations in participants with Colorectal Cancer (CRC).",[28],[89,90,91,92,93,94,80],"Metastatic disease","Immunotherapy","Liver metastasis","Mismatch-repair-proficient","Antibody targeting","Colorectal Cancer",{"date":39,"type":40},{"date":97,"type":40},"2025-03-12",{"date":99,"type":21},"2028-09-29",{"name":101,"class":72},"AstraZeneca",76,{"id":104,"slug":105,"hasResults":12,"nctId":106,"briefTitle":107,"officialTitle":108,"acronym":109,"eligibilityCriteria":110,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":111,"targetDuration":4,"studyType":22,"phases":113,"briefSummary":115,"conditions":116,"keywords":117,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":123,"lastUpdatePostDateStruct":124,"startDateStruct":126,"completionDateStruct":128,"leadSponsor":130,"locationsCount":132},"100535501","phase-3-study-of-sotorasib-panitumumab-and-folfiri-versus-folfiri-with-or-without-bevacizumab-awwb-in-treatment-nave-participants-with-metastatic-colorectal-cancer-with-kras-pg12c-mutation-100535501","NCT06252649","Study of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb in Treatment-naïve Participants With Metastatic Colorectal Cancer With KRAS p.G12C Mutation","Phase 3 Multicenter, Randomized, Open-label, Active-controlled Study of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb for Treatment-naïve Subjects With Metastatic Colorectal Cancer With KRAS p.G12C Mutation (CodeBreaK 301)","CodeBreaK 301","Inclusion Criteria:\n\n* Pathologically documented metastatic colorectal adenocarcinoma with KRAS p.G12C mutation by a locally validated assay.\n* Central laboratory detection of KRAS p.G12C mutation.\n* Measurable metastatic disease per RECIST v1.1 criteria.\n* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1.\n* Adequate organ function.\n\nExclusion Criteria:\n\n* Active, untreated brain metastases.\n* Leptomeningeal disease\n* Previous treatment with a KRAS p.G12C inhibitor\n* History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline CT scan",{"count":112,"type":21},450,[114],"PHASE3","The aim of this study is to compare progression free survival (PFS) in treatment-naïve participants with KRAS p.G12C mutated metastatic colorectal cancer (mCRC) receiving sotorasib, panitumumab and FOLFIRI vs FOLFIRI with or without bevacizumab-awwb.",[28],[118,119,120,121,122],"Sotorasib","Panitumumab","FOLFIRI","Bevacizumab-awwb","Oncology","2026-07-01",{"date":125,"type":40},"2026-07-02",{"date":127,"type":40},"2024-07-17",{"date":129,"type":21},"2032-04-25",{"name":131,"class":72},"Amgen",292,{"id":134,"slug":135,"hasResults":12,"nctId":136,"briefTitle":137,"officialTitle":138,"acronym":4,"eligibilityCriteria":139,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":140,"targetDuration":4,"studyType":22,"phases":142,"briefSummary":143,"conditions":144,"keywords":145,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":153,"lastUpdatePostDateStruct":154,"startDateStruct":155,"completionDateStruct":157,"leadSponsor":159,"locationsCount":161},"100599064","phase-1-a-clinical-study-to-test-if-an-investigational-treatment-called-bnt314-when-used-in-combination-with-another-investigational-treatment-pumitamig-bnt327-and-chemotherapy-is-beneficial-and-safe-for-patients-with-advanced-colorectal-cancer-100599064","NCT07079631","A Clinical Study to Test if an Investigational Treatment Called BNT314 When Used in Combination With Another Investigational Treatment Pumitamig (BNT327) and Chemotherapy, is Beneficial and Safe for Patients With Advanced Colorectal Cancer","A Phase I\u002FII, Randomized, Multi-site Trial to Investigate the Efficacy and Safety of BNT314 in Combination With Pumitamig and Chemotherapy in Participants With Metastatic Colorectal Cancer","Key Inclusion Criteria:\n\n* Have unresectable histologically confirmed adenocarcinoma of the colon or rectum.\n* Have confirmed non-microsatellite instability-high (non-MSI-H)\u002FpMMR mCRC per Food and Drug Administration (FDA)\u002FEuropean Commission (EC) approved test or based on local testing.\n* Have measurable disease defined by RECIST v1.1.\n* Must provide a tumor tissue sample (formalin-fixed, paraffin-embedded or tissue slides) collected before C1D1 for enrollment. A newly obtained tumor sample is preferred. If it is not feasible to obtain a recent tumor sample, participants can provide archival tumor tissue (less than 2 years prior treatment).\n* Have Eastern Cooperative Oncology Group Performance Status of 0 or 1.\n* Have a life expectancy of ≥12 weeks.\n* Have an adequate organ and bone marrow function within ≤7 days of Day 1 as defined in the protocol.\n* Have had an adequate previous treatment washout period before randomization\u002Fenrollment as defined in the protocol.\n\nInclusion criteria applicable to only protocol-specific cohorts:\n\n* Have histologically confirmed metastatic colorectal cancer and radiographically documented disease progression after ≥2 prior lines of systemic therapy for metastatic disease as defined in the protocol.\n* Have progressed following first-line chemotherapy as specified in the protocol.\n* Have not received prior systemic therapy for MSS\u002FpMMR mCRC. Participants who received chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease in the neoadjuvant or adjuvant setting are eligible for the study if therapy was completed at least 6 months prior to initiation of study treatment.\n\nOther cohort-specific inclusion criteria apply.\n\nKey Exclusion Criteria:\n\n* Confirmed MSI-H\u002Fdeficient mismatch repair mCRC (per FDA\u002FCE approved test or based on local testing).\n* Prior treatment with epithelial cell-adhesion molecule or 4-1BB targeted or immunotherapy.\n* Prior treatment with immune checkpoint inhibitors or programmed death-ligand 1 (PD\\[L\\]-1)\u002Fvascular endothelial growth factor bispecific antibody.\n* Is a candidate to locoregional treatment (including surgical resection, stereotactic radiation therapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control (sometimes described as \"radical\" intent), per investigator's assessment.\n* Have uncontrolled or significant cardiovascular disease as specified in the protocol.\n* Have left ventricular ejection fraction \\\u003C50% by echocardiogram or multigated acquisition within 28 days before randomization\u002Fenrollment.\n* Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization\u002Fenrollment.\n* Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. Participants with untreated, asymptomatic brain metastases for whom local therapy is not indicated per SoC may be eligible if neurologically stable and (if deemed necessary by the investigator). Except for brain metastases history, any participants at imminent risk for spinal cord compression or leptomeningeal disease are not eligible.\n* Have unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline toxicities that have resolved with sequelae (e.g., tracheostomy, chronic use of feeding tube, replacement hormones) are allowed, if not associated with increased risk of complications per investigator's assessment.\n* Participants in Part B or C who fulfill one of the conditions:\n\n  * Prior treatment with anticancer therapies (as defined in the protocol) with unusual toxicity, or\n  * Known dihydropyrimidine dehydrogenase (DPD) deficiency, testing performed according to the local guidelines. If not tested, lack of DPD activity must be tested for the participants who have not received anticancer therapies (as defined in the protocol) in the prior lines of treatment; testing should be performed according to the local guidelines.\n* Have a history of another primary malignancy within 2 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated (adjuvant hormone therapy for malignancies at low risk of relapse is allowed) or have a known additional malignancy that is progressing or requires treatment.\n* Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.\n* Have 24-h urine protein excretion ≥1 g. If qualitative urine protein is ≤1+, a 24-h urine protein quantitative test is not required.\n* Have active autoimmune disease or a history of autoimmune disease (myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, vasculitis, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis) with a risk of exacerbation following PD-L1 inhibition or have an immune deficiency (allogeneic hematopoietic stem cell transplantation or organ transplantation). Participants with protocol-specified conditions may be eligible.\n* Have serious non-healing wounds, ulcers, or bone fractures. This includes history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess or esophageal and gastric varices, acute gastrointestinal bleeding for which an interval of 6 months must pass before enrollment into this study. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation\u002Ffistula and\u002For the underlying process causing the fistula\u002Fperforation.\n* Have evidence of major coagulation disorders or other significant risks of hemorrhage as specified in the protocol.\n\nNOTE: Other protocol defined Inclusion\u002FExclusion criteria apply.",{"count":141,"type":21},482,[24,25],"This randomized, multi-site, three-part study will test a new treatment called BNT314, which is designed to help the body's own defense to fight cancer in combination with another new treatment (pumitamig, which is a cancer immunotherapy drug also known as BNT327 and PM8002) and chemotherapy in participants with metastatic colorectal cancer (mCRC).",[28],[146,147,148,149,150,90,151,152],"Microsatellite stable or mismatch repair proficient (MSS\u002FpMMR) tumors","Immune checkpoint inhibitor","Programmed death-ligand 1 (PD-L1)","Vascular endothelial growth factor-A (VEGF-A)","Bispecific antibody","Combination chemotherapy","Dose optimization","2026-06-30",{"date":123,"type":40},{"date":156,"type":40},"2025-07-18",{"date":158,"type":21},"2032-12",{"name":160,"class":72},"BioNTech SE",14,{"id":163,"slug":4,"hasResults":12,"nctId":52,"briefTitle":53,"officialTitle":54,"acronym":55,"eligibilityCriteria":56,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":164,"targetDuration":4,"studyType":22,"phases":165,"briefSummary":60,"conditions":166,"keywords":167,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":168,"lastUpdatePostDateStruct":169,"startDateStruct":170,"completionDateStruct":171,"leadSponsor":172,"locationsCount":173},"100579143",{"count":58,"type":21},[25],[28],[28,63,64],"2026-06-26",{"date":153,"type":40},{"date":67,"type":40},{"date":69,"type":21},{"name":71,"class":72},53,{"id":175,"slug":176,"hasResults":12,"nctId":177,"briefTitle":178,"officialTitle":178,"acronym":4,"eligibilityCriteria":179,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":180,"targetDuration":4,"studyType":22,"phases":182,"briefSummary":183,"conditions":184,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":186,"lastUpdatePostDateStruct":187,"startDateStruct":188,"completionDateStruct":190,"leadSponsor":192,"locationsCount":195},"100547763","phase-1-a-multicenter-phase-1b2-study-of-adagrasib-cetuximab-and-cemiplimab-for-metastatic-colorectal-cancer-harboring-kras-g12c-mutations-100547763","NCT06412198","A Multicenter Phase 1b\u002F2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations","Inclusion Criteria:\n\n* Histologically confirmed diagnosis of advanced\u002Fmetastatic microsatellite stable colorectal cancer with KRASG12C mutation with 1+ prior line(s) of therapy\n* Confirmed KRASG12C mutation status. If a molecular profiling report is not available, a representative paraffin-embedded tumor block or a minimum of 10 unstained slides will be requested for retrospective KRASG12C mutation testing.\n* Unresectable or metastatic disease.\n* Participants must have received at least one prior line of chemotherapy for metastatic disease with progression on treatment or intolerance to therapy.\n* Presence of measurable disease per RECIST 1.1\n* Willingness to participate in on-study related procedures, including mandatory biopsies (one baseline and one on-treatment biopsy).\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of the proposed combination in patients \\\u003C18 years of age, children are excluded from this study.\n* Able to take oral medications.\n* Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy or investigational agent) and radiation therapy discontinued at least 7 days before first dose.\n* Recovery from the treatment-related adverse effects of prior therapy at the time of enrollment to ≤ Grade 1 (excluding alopecia and prior oxaliplatin-induced neuropathy).\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n* Laboratory values within the screening period:\n\n  * Absolute neutrophil count ≥ 1,000\u002Fmm3 (≥ 1.0 x 109\u002FL)\n  * Platelet count ≥ 100,000\u002Fmm3 (≥ 100 x 109\u002FL)\n  * Hemoglobin ≥ 9 g\u002FdL, in the absence of transfusions for at least 2 weeks\n  * Total bilirubin ≤ 1.5x upper limit of normal (ULN) (if associated with Gilbert's disease or UGT1A1\\*28 homozygosity, ≤ 3x ULN)\n  * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0x ULN (if associated with liver metastases ≤5x ULN)\n  * Calculated creatinine clearance (determined as per Cockcroft-Gault) ≥ 60mL\u002Fmin at screening\n* Completed informed consent process, including signing of IRB-approved informed consent form.\n* Willing and able to comply with clinical trial instructions and requirements. Individuals lacking the ability, based on reasonable medical judgment, to understand and appreciate the nature and consequences of participation in this study will not be eligible for participation.\n* Participants who are biologically capable of having children and sexually active must agree to use an acceptable method of contraception for the duration of the treatment period and for at least 6 months after the last dose of study treatment. The Investigator will counsel the patient on selection of contraception method and instruct the participant in its consistent and correct use. Examples of acceptable forms of contraception include:\n\n  * Oral, inserted, injected or implanted hormonal methods of contraception, provided it has been used for an adequate period of time to ensure effectiveness.\n  * Correctly placed copper containing intrauterine device (IUD).\n  * Male condom or female condom used WITH a spermicide.\n  * Male sterilization with confirmed absence of sperm in the post-vasectomy ejaculate.\n  * Bilateral tubal ligation or bilateral salpingectomy.\n* The Investigator will instruct the participant to call immediately if the selected birth control method is discontinued or if pregnancy is known or suspected.\n\n  * Note: Women are considered post-menopausal and\u002For not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 months ago. In case of any ambiguity, the reproductive status of the woman should be confirmed by hormone level assessment.\n\nExclusion Criteria:\n\n* Prior PD1 or CTLA4 inhibition therapy\n* Prior KRASG12C inhibition therapy\n* 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\n* Active autoimmune disease that has required systemic treatment in the past 2 years (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 not considered a form of systemic treatment\n* Active brain metastases, unless adequately treated and participant is neurologically stable (except for residual symptoms of central nervous system treatment) for at least 2 weeks prior to enrollment without corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent)\n* Ongoing need for a medication with any of the following characteristics that cannot be switched to alternative treatment within 10 days prior to study entry: known risk of QTc prolongation or Torsades de Pointes; substrate of CYP3A with a narrow therapeutic index; strong inducer or inhibitor of CYP3A and\u002For P-gp; strong inhibitor of BCRP; strong inhibitor or inducer of CYP2C19; and proton pump inhibitors.\n\nNote: one dose of propofol, midazolam, and\u002For fentanyl under a monitored setting during IR guided biopsies is allowed.\n\n* Pregnancy. Women of child-bearing potential must have a negative serum or urine pregnancy test during screening\n* Breast-feeding or planning to breast feed during the study or within 6 months after end of treatment.\n* Participants with symptomatic leptomeningeal disease.\n* Major surgery within 4 weeks of first dose of any study drug.\n* History of intestinal disease or major gastric surgery likely to alter absorption of study treatment, to be determined by the treating physician\n* Known human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B (HBV) or C (HCV) infection as tested in a CLIA certified lab using a positive HIV antibody test. For Hepatitis B and C, an antigen that is drawn and positive. Note that the following are permitted:\n* Participants treated for HIV with no detectable viral load on current regimen for at least 1 month prior to randomization;\n* Note: Please refer to exclusion criteria regarding drug-drug interactions of concomitant anti-HIV agents, and in particular CYP3A substrates.\n* Participants with prior HBV infections who are:\n* considered to have past or resolved HBV infection, defined as the presence of hepatitis B core antibody \\[HBcAb\\] and absence of hepatitis B surface antigen \\[HBsAg\\]; or\n* considered to be in an inactive HBV carrier state, defined as HBsAg-positive with normal ALT, and HBV DNA \\\u003C 2,000 IU\u002FmL or \\\u003C 10,000 copies\u002FmL;\n* Note: For participants in an inactive HBV carrier state or with a resolved HBV infection, the risk of HBV reactivation should be considered and the need for anti-HBV prophylaxis prior to randomization should be carefully assessed in accordance with local guidelines.\n* Participants treated for HCV with no detectable viral load.\n* Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical history, including laboratory results, which, in the investigator's opinion, would be likely to interfere with the participant's participation in the study, or with the interpretation of results.",{"count":181,"type":21},31,[24,25],"To learn if the drug combination of adagrasib, cetuximab, and cemiplimab can help to control metastatic CRC with KRAS G12C mutations.",[28,185],"KRAS G12C Mutations","2026-06-24",{"date":168,"type":40},{"date":189,"type":40},"2024-08-28",{"date":191,"type":21},"2029-03-01",{"name":193,"class":194},"M.D. Anderson Cancer Center","OTHER",2,{"id":197,"slug":198,"hasResults":12,"nctId":199,"briefTitle":200,"officialTitle":201,"acronym":4,"eligibilityCriteria":202,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":203,"targetDuration":4,"studyType":22,"phases":205,"briefSummary":206,"conditions":207,"keywords":208,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":210,"lastUpdatePostDateStruct":211,"startDateStruct":213,"completionDateStruct":215,"leadSponsor":217,"locationsCount":219},"100433830","phase-1-a-study-evaluating-the-safety-and-efficacy-of-targeted-therapies-in-subpopulations-of-patients-with-metastatic-colorectal-cancer-intrinsic-100433830","NCT04929223","A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)","A Phase I\u002FIb Global, Multicenter, Open-label Umbrella Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)","Inclusion Criteria\n\n* Signed cohort-specific Informed Consent Form\n* Age \\>= 18 years at time of signing Informed Consent Form\n* Biomarker eligibility as determined by:\n\n  * A validated test approved by local health authorities for detection of the specified biomarkers\u002Fmutations.\n  * A validated test performed at a College of American Pathologists\u002Fclinical laboratory improvement amendments (CAP\u002FCLIA) -certified or equivalently accredited diagnostic laboratory using a validated test for detection of the specified biomarkers.\n  * Prior test results completed before signing cohort-specific Informed Consent Form or local test results generated prior to or during screening, and availability of a full report of the testing results OR\n  * Blood-based FoundationOne Liquid CDx biomarker eligibility test result generated prior to or during screening or, in case of re-enrollment after treatment discontinuation, prior to starting a new anti-cancer therapy.\n* Eastern Cooperative Oncology Group (ECOG) Performance Status of \\\u003C= 1\n* Life expectancy \\>= 3 months, as determined by the investigator\n* Histologically confirmed adenocarcinoma originating from the colon or rectum\n* Metastatic disease\n* Prior therapies for metastatic disease\n* Ability to comply with the study protocol, in the investigators judgment\n* Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)\n* Baseline tumor tissue samples will be collected from all participants for exploratory biomarker research\n* Adequate hematologic and organ function within 14 days prior to initiation of study treatment\n* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures\n* For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm\n\nExclusion Criteria\n\n* Current participation or enrollment in another interventional clinical trial. Participants who are participating in the follow-up period of an interventional clinical trial are eligible for the study.\n* Any systemic anti-cancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment\n* Treatment with investigational therapy within 28 days prior to initiation of study treatment\n* Pregnant or breastfeeding, or intending to become pregnant during the study\n* History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study\n* Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety\n* Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of study treatment\n* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)\n* Uncontrolled tumor-related pain\n* Uncontrolled or symptomatic hypercalcemia\n* Clinically significant and active liver disease\n* Negative HIV test at screening, with the following exception: Participants with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count greater than or equal to 200\u002FuL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months.\n* Symptomatic, untreated, or actively progressing CNS metastases\n* History of leptomeningeal disease or carcinomatous meningitis\n* History of malignancy other than CRC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death\n* Any other disease, unresolved toxicity from prior therapy, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk from treatment complications\n* Requirement for treatment with any medicinal product that contraindicates the use of any of the study treatments, may interfere with the planned treatment, affects participant compliance, or puts the patient at higher risk for treatment-related complications",{"count":204,"type":21},542,[24],"This open-label, exploratory study is designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or combinations, in participants with metastatic colorectal cancer (mCRC) whose tumors are biomarker positive as per treatment arm-specific definition. Eligible participants with mCRC will be enrolled into specific treatment arms based on their biomarker assay results.",[28],[209],"KRAS G12C","2026-06-19",{"date":212,"type":40},"2026-06-23",{"date":214,"type":40},"2021-10-22",{"date":216,"type":21},"2030-08-31",{"name":218,"class":72},"Hoffmann-La Roche",84,{"id":221,"slug":222,"hasResults":12,"nctId":223,"briefTitle":224,"officialTitle":225,"acronym":226,"eligibilityCriteria":227,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":228,"targetDuration":4,"studyType":22,"phases":230,"briefSummary":231,"conditions":232,"keywords":235,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":239,"lastUpdatePostDateStruct":240,"startDateStruct":242,"completionDateStruct":244,"leadSponsor":246,"locationsCount":48},"100612598","phase-1-a-fih-phase-iiia-trial-assessing-feasibility-of-administrations-of-til-based-immunotherapy-in-patients-with-metastatic-crc-and-pc-100612598","NCT07255664","A FIH, Phase I\u002FIIa, Trial Assessing Feasibility of Administrations of TIL-based Immunotherapy in Patients With Metastatic CRC and PC","A FIH, Phase I\u002FIIa, Open-label Trial Assessing Safety, Tolerability, and Feasibility of Repeated Administrations of a Novel Autologous TIL-based Immunotherapy in Patients With Metastatic Colorectal or Prostate Cancer","ProbeTILity","Inclusion Criteria:\n\n* Patient (female or male) has signed informed consent according to ICH\u002FGCP and national\u002Flocal regulations prior to any trial-specific procedure.\n* Patient is 18 years or older at the time of signing the informed consent form.\n* Patient must live in an area where a hospital for care can be reached within a maximum of 50 km.\n* Patient has histological or cytological confirmation of:\n\n  * colorectal cancer, which is stage IV (any T \u002F any N \u002F M1), not amenable to curative surgery, OR\n  * prostate cancer, which is stage III locally advanced, not amenable to curative surgery (T3-4 \u002F N0 \u002F M0 or any T \u002F N1 \u002F M0), or stage IV metastatic (any T \u002F any N \u002F M1)\n* Patient has received all lines of therapy that\n\n  * are considered SOC for the patient's indication according to applicable European\u002Fnational professional society medical guidelines and local medical practice at time of enrollment\n  * are available via the national health insurance system and the patient is considered eligible for but led to insufficient response or were medically not justified or refused by the patient.\n* Patient has confirmed disease progression by radiologic imaging from the previous line of therapy.\n* Patient has sufficient amount of previously not irradiated tumor tissue in adequate quality for TIL harvest and expansion, i.e., either:\n\n  * Primary or metastatic lesion has been selected for surgery (e.g., to reduce tumor burden, pain relief), Or\n  * Patient has consented to surgery for the purpose of tissue harvesting for TIL expansion and is considered suitable to undergo surgery for this purpose. Note: Patients with a non-justifiable anesthesiologic and\u002For surgical risk, as determined by the investigator, should be excluded\n* Patient has a least one measurable or assessable lesion according to RECIST 1.1 remaining after tumor resection for CC-38 manufacturing has been performed.\n* Patient has ECOG performance status of 0 or 1.\n* Patient has a minimum life expectancy of 6 months in the opinion of the investigator from the time of consent date.\n* Patient has adequate bone marrow, hepatic and renal function in the opinion of the investigator:\n\n  1. Hemoglobin ≥ 9.0 g\u002FdL,\n  2. Absolute neutrophil count (ANC) ≥ 1.0 x 109 \u002FL,\n  3. Platelets ≥ 80 x 109 \u002FL,\n  4. Calculated creatinine clearance ≥ 50 mL\u002Fmin (Cockcroft-Gault formula),\n  5. Serum bilirubin ≤ 1.5 x ULN (or ≤ 2.5 x ULN in the presence of documented Gilbert's Syndrome \\[unconjugated hyperbilirubinemia\\] or liver metastases),\n  6. AST\u002F ALT and alkaline phosphatase ≤ 2.5 x ULN (or ≤5 times ULN in the presence of bone and\u002For liver metastases), ALP ≤ 2.5 x ULN,\n  7. International normalized ration (INR) ≤ 1.5 or prothrombin time (PT) ≤ ULN + 4 seconds.\n* Female patients must be post-menopausal or use contraceptive methods with a failure rate of \\\u003C 1% 6 months after last administration of CC-38, whatever is later, to prevent pregnancy. Male patients with fertile female partners must be willing to use condoms with spermicide, and the fertile partner must use contraceptive methods with a failure rate of \\\u003C 1% for the same time period. Male patients must also refrain from donating sperm for the same time period.\n* Successful tumor tissue sampling by surgery, including presence of TILs in the tumor tissue in the pathological evaluation.\n* Successful TIL expansion defined as obtaining the final CC-38 drug product\n\nExclusion Criteria:\n\n* Patient as any of the following condition:\n\n  1. Congestive heart failure NYHA class III or IV,\n  2. myocardial infarction or coronary artery bypass graft within 6 months prior to enrollment,\n  3. history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration,\n  4. history of severe non-ischemic cardiomyopathy,\n  5. uncontrolled blood pressure as defined as systolic \\> 160 mmHg, diastolic \\> 100 mmHg within 3 months prior to enrollment,\n  6. left ventricular ejection fraction (LVEF) \\\u003C 45% as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan,\n  7. any other clinically significant cardiovascular events such as unstable angina, angioplasty, stroke, or transient ischemic attack (TIA) within less than 6 months before enrolment,\n  8. other conditions that the treating physicians believe may endanger the health of the patients by their participation in this clinical trial.\n* Patient has any of the following pulmonary conditions:\n\n  1. Forced expiratory volume in 1 second (FEV1)\\\u003C60%,\n  2. Active obstructive chronic pulmonary disease,\n  3. oxygen dependence as defined by a blood oxygen saturation that can only be maintained above 92% by oxygen inhalation (finger oxygen detection method),\n  4. other pulmonary conditions that increase the anesthesiologic risk.\n* Patient has a current or history of central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression,\n* Patient has ulcers in the upper GI tract, untreated or incompletely treated esophageal varices with high risk of bleeding in the investigator's discretion.\n* Patient requiring therapeutic anticoagulant therapy or having other increased risk of bleeding events.\n* Patient has any severe acute or chronic medical condition that places the patient at increased risk or interferes with the interpretation of trial results in the opinion of the investigator.\n* Patient has any form of primary immunodeficiency (such as severe combined immunodeficiency disease \\[SCID\\] and acquired immune deficiency syndrome \\[AIDS\\]).\n* Patient has active or history of autoimmune or inflammatory disorders. Note: Patients may be eligible if they have been assessed in discussion between Principal Investigator, Chief Medical Officer and Senior Medical Consultant as not posing an increased risk to the patient.\n* Patient receiving immunosuppressive concomitant medications (≥ 10 mg prednisone daily or other equivalent). Steroid medications are allowed if they are used as substitution or are administrated topically or as inhalations.\n* Patient has received an organ and\u002For allogenic stem cell transplant.\n* Patient has known acute or chronic infection with hepatitis B or C virus.\n* Patient has known HIV infection (seropositive for HIV antibody).\n* Patient has known infection with syphilis.\n* Patient has known bone-marrow aplasia.\n* Patient has known (chronical) urinary tract infection and\u002F or acute urothelial toxicity from previous cytotoxic chemotherapy or radiation therapy or urinary flow obstructions.\n* Female patient, who is pregnant or breast-feeding, or plan to become pregnant within 12 months after cyclophosphamide or 6 months after last dose of CC-38, whichever last. Women of childbearing potential must have a negative pregnancy test at screening and before every CC-38 application.\n* Patient is unable to comply with trial procedures, restrictions, or requirements.\n* Patient received last previous systemic cancer treatment (including anti-testosterone treatment) within less than 4 weeks prior enrollment.\n\nNote: Bridging therapies (specified in trial design \\[section 2 - subsection: screening and TIL harvesting\\]) after TIL harvesting and before CC-38 administration are permitted after consultation between Principal Investigator, Chief Medical Officer and Senior Medical Consultant.\n\n* Patient received last palliative radiotherapy within less than 4 weeks prior enrollment - where RECIST 1.1 evaluable metastases are within the radiation area.\n* Patient received minor surgery (as judged by the investigator, i.e., port implantation) within less than 3 weeks prior enrollment.\n* Patient with AEs from previous treatment that have not recovered to CTCAE v5.0 ≤ grade 1 Note: Clinically insignificant grade 2 AEs that may be allowable if discussed between and approved by Principal Investigator, Chief Medical Officer and Senior Medical Consultant.\n* Patient participates in any other interventional clinical trial or has been treated with any investigational research products within 4 weeks prior to the initiation of screening.\n* Patient has bone metastasis only.\n* Patient has known hypersensitivity to any component of the trial regimen.\n* For colorectal cancer: Patient has been diagnosed with histologically or cytologically proven BRAF-V600 positive CRC.\n* Patient has any further contraindication to the IMP pembrolizumab or any of the auxiliary medicinal products (i.e., IL-2, cyclophosphamide, uromitexan) as per current EU SmPCs to the respective product.",{"count":229,"type":21},12,[24,25],"This is a First-In-Human trial investigating a novel expansion protocol of an ATIMP (CC-38), composed of autologous TIL.",[28,233,234],"Prostate Cancer Metastatic","Prostate Cancer Locally Advanced",[236,237,238,90],"mCRC","aPC","TIL","2026-06-18",{"date":241,"type":40},"2026-06-22",{"date":243,"type":40},"2025-11-13",{"date":245,"type":21},"2029-04",{"name":247,"class":72},"CuraCell TX AB",{"id":249,"slug":250,"hasResults":12,"nctId":251,"briefTitle":252,"officialTitle":253,"acronym":4,"eligibilityCriteria":254,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":255,"targetDuration":4,"studyType":22,"phases":257,"briefSummary":258,"conditions":259,"keywords":270,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":239,"lastUpdatePostDateStruct":288,"startDateStruct":289,"completionDateStruct":291,"leadSponsor":293,"locationsCount":295},"100564176","phase-1-open-label-study-of-bbo-10203-in-subjects-with-advanced-solid-tumors-100564176","NCT06625775","Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors","A Phase 1a\u002F1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-10203 in Subjects With Advanced Solid Tumors (The BREAKER-101 Study)","Inclusion Criteria:\n\n* Locally advanced and unresectable or metastatic HER2-positive advanced breast cancer (aBC), HR-positive\u002FHER2-negative advanced breast cancer, KRAS mutant advanced colorectal cancer (aCRC), or KRAS mutant advanced non-small cell lung cancer (aNSCLC)\n* Measurable disease by RECIST v1.1 (except for HR-positive HER2-negative aBC where evaluable bone-only disease is permitted)\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1\n* Adequate LVEF assessed by ECHO or MUGA (BBO-10203 + Trastuzumab cohorts only)\n* Stable brain metastases\n* Patients with HER2-positive aBC: Must have had at least 2 prior lines of anti-HER2-directed therapy. Only 1 prior line is acceptable where there is no other regionally available standard of care (SoC)\n* Monotherapy Cohort patients with HR-positive, HER2-negative aBC, KRAS mutant aCRC or aNSCLC: Must have progression on, or disease recurrence after at least one line of SOC treatment or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from SoC therapy\n* BBO-10203 + Fulvestrant combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, must have been treated with a CDK4\u002F6i\n* BBO-10203 + Fulvestrant + ribociclib combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, no prior systemic therapy in the aBC setting permitted\n* BBO-10203 + FOLFOX + Bevacizumab combination cohort patients with KRAS mutant aCRC: One prior line of irinotecan-containing therapy for locally advanced or metastatic CRC is allowed but not required\n\nExclusion Criteria:\n\n* Patients with KRAS mutant aCRC who have KRAS G12R mutation, BRAFV600E mutation, HER2amp, or dMMR\u002FMSI-H tumors\n* Patients with KRAS mutant aNSCLC who have KRAS G12R mutation, or tumors with other targetable driver mutations (eg, EGFR, anaplastic lymphoma kinase, ROS1\u002FBRAF\u002FRET\u002FMET\u002FEGFR exon20 insertion\u002FNTRK\u002FHER2)\n* Patients with untreated and\u002For non-stable brain metastases\n\nOther inclusion\u002Fexclusion criteria are specified in the protocol",{"count":256,"type":21},392,[24],"First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination with other anti-cancer agents in patients with advanced solid tumors.",[260,261,262,263,264,265,266,28,267,268,269],"Solid Tumor, Adult","Metastatic Breast Cancer","Advanced Breast Cancer","HER2 Mutation-Related Tumors","HER2-positive Metastatic Breast Cancer","KRAS Mutant Metastatic Colorectal Cancer","Metastatic Lung Cancer","Advanced Lung Cancer","HR-positive, HER2-negative Advanced Breast Cancer","HER2-positive Advanced Breast Cancer",[271,272,273,274,275,276,277,278,279,280,281,282,283,284,285,286,287],"BREAKER-101","BridgeBio Oncology Therapeutics","BBOT","Phase1","Phase 1a\u002F1b","Trastuzumab","Breast","Colorectal","Non-Small Cell Lung Cancer","CRC","NSCLC","Metastatic Cancer","Advanced Cancer","HER2-positive","HR-positive","HR-positive, HER2-negative","HER2-negative",{"date":212,"type":40},{"date":290,"type":40},"2024-10-29",{"date":292,"type":21},"2028-11",{"name":294,"class":72},"TheRas, Inc., d\u002Fb\u002Fa BBOT (BridgeBio Oncology Therapeutics)",40,{"id":297,"slug":298,"hasResults":12,"nctId":299,"briefTitle":300,"officialTitle":301,"acronym":4,"eligibilityCriteria":302,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":303,"targetDuration":4,"studyType":22,"phases":304,"briefSummary":305,"conditions":306,"keywords":307,"overallStatus":311,"whyStopped":4,"lastUpdateSubmitDate":312,"lastUpdatePostDateStruct":313,"startDateStruct":314,"completionDateStruct":316,"leadSponsor":318,"locationsCount":48},"100644338","phase-2-tovecimig-plus-folfiri-in-second-line-metastatic-colorectal-cancer-100644338","NCT07662031","Tovecimig Plus FOLFIRI in Second Line Metastatic Colorectal Cancer","A Phase 2 Clinical Trial of Tovecimig Plus FOLFIRI in Second Line Metastatic Colorectal Cancer","Inclusion Criteria:\n\n* Histologically or cytologically confirmed CRC.\n* Patient must have undergone resection of his\u002Fher primary tumor either as part of treatment for early stage disease with subsequent metastatic progression or due to a tumor related complication in the metastatic setting (e.g. bowel obstruction).\n* Measurable disease per RECIST 1.1.\n* Patient must have advanced or metastatic disease, and have progressed on one line of standard of care therapy in the advanced\u002Fmetastatic setting\n* At least 18 years of age.\n* ECOG performance status ≤ 2\n* Adequate bone marrow and organ function as defined below:\n\n  * Absolute neutrophil count ≥ 1.5 K\u002Fcumm\n  * Platelets ≥ 100 K\u002Fcumm\n  * Hemoglobin ≥ 8.0 g\u002FdL\n  * Total bilirubin ≤ 1.5 x IULN or ≤ 2.0 mg\u002FdL in presence of liver metastases\n  * AST(SGOT)\u002FALT(SGPT) ≤ 3x IULN or ≤ 5x IULN in presence of liver metastases\n  * Creatinine clearance \\> 50 mL\u002Fmin by Cockcroft-Gault\n* The effects of Tovecimig and FOLFIRI on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months after the last dose of Tovecimig or any component of FOLFIRI. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s\u002Fhe must inform her treating physician immediately.\n* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.\n\nExclusion Criteria:\n\n* Patients with MSI-H status.\n* Intact primary tumor that has not been resected.\n* More than one line of prior therapy for advanced or metastatic CRC.\n\n  \\*If FOLFIRI\u002FFOLFOXIRI was given in the first line, it must have been completed ≥ 6 months before study start date.\n* Surgery or major procedure, or systemic anticancer therapy within 4 weeks prior to C1D1.\n* Radiation therapy within 2 weeks prior to C1D1.\n* Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.\n* Receipt of any other investigational agents within 4 weeks prior to C1D1, with exception of investigational imaging agents.\n* Patients with untreated brain metastases. Patients with treated brain metastases are allowed if post-treatment brain-imaging after CNS-directed therapy shows no evidence of progression.\n* Prior history of diseases\u002Fconditions that elevates the patient's risk of hemorrhage, such as a bleeding diatheses, history of prior bowel perforation, or clinically significant active bleeding (i.e. hemoptysis larger than a tablespoon within 3 weeks prior to C1D1).\n* Recent history of paracentesis (within 3 weeks prior to C1D1) or current indwelling catheter.\n* A history of hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to Tovecimig (i.e. humanized\u002Fhuman monoclonal antibody drugs), FOFLIRI, or other agents used in the study.\n* Use of anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylaxis) purpose within 10 days of C1D1.\n* Use of aspirin, other NSAIDs (i.e. naproxen, ibuprofen), or other antiplatelet drugs within 10 days of C1D1.\n* Uncontrolled intercurrent illness\u002Finfection requiring ongoing systemic antibiotics, antivirus drugs, or other uncontrolled active acute infectious diseases.\n* A history of CHF (NYHA class II or higher) with 5 years prior to C1D1, LVEF \\\u003C 50% on screening TTE\u002FMUGA, uncontrolled hypertension (defined as SBP\u002FDBP greater than 140\u002F90 despite best supportive care at any time during screening), pulmonary hypertension, myocardial infarction, uncontrolled arrhythmia, unstable angina, or any significant valvular disease.\n* Pregnant and\u002For breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of C1D1.\n* HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.\n* Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.\n* History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.",{"count":7,"type":21},[25],"This is an open-label Phase 2 study to evaluate the safety and efficacy of Tovecimig combined with FOLFIRI in patients who have received one prior line of therapy for advanced or metastatic colorectal cancer (CRC).",[94,28],[308,309,310],"Tovecimig","Colorectal cancer","Microsatellite stable","NOT_YET_RECRUITING","2026-06-17",{"date":212,"type":40},{"date":315,"type":21},"2026-08-31",{"date":317,"type":21},"2032-08-31",{"name":319,"class":194},"Washington University School of Medicine",{"id":321,"slug":322,"hasResults":12,"nctId":323,"briefTitle":324,"officialTitle":325,"acronym":4,"eligibilityCriteria":326,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":327,"targetDuration":4,"studyType":329,"phases":4,"briefSummary":330,"conditions":331,"keywords":4,"overallStatus":311,"whyStopped":4,"lastUpdateSubmitDate":312,"lastUpdatePostDateStruct":332,"startDateStruct":333,"completionDateStruct":335,"leadSponsor":337,"locationsCount":4},"100641121","a-study-of-fruquintinib-in-adults-with-metastatic-colorectal-cancer-in-poland-100641121","NCT07623174","A Study of Fruquintinib in Adults With Metastatic Colorectal Cancer in Poland","FRAMEWORK-CRC: Fruquintinib Real-World Outcomes in mCRC - A Prospective Study of One-Year Progression-Free Survival and Overall Survival in Polish Patients","Inclusion Criteria:\n\n1. Adult participants (aged 18 years and older) with mCRC who are eligible for treatment with fruquintinib under the national drug program B.4 and will receive fruquintinib as third or subsequent line treatment after progression on or intolerance to trifluride\u002Ftipiracil.\n2. Participants who signed informed consent to participate in the study at the time of enrollment and prior to the fruquintinib treatment initiation.\n3. Participants for whom adequate medical records are available to support the data collection requirements.\n\nExclusion Criteria:\n\n1\\. Participant currently participates or plans to participate in an interventional clinical trial.",{"count":328,"type":21},110,"OBSERVATIONAL","Metastatic colorectal cancer or mCRC is a cancer that starts in the parts of the large intestine (the colon or rectum) and has already spread to other parts of the body. This cancer can be hard to treat because it can behave differently from one person to another. Over time, treatments may stop working, and side effects can build up. In later treatment stages, there are only a few standard medicine options available. Because of this, studies often look at both how long people live and how treatment affects quality of life.\n\nThe main aim of this study is to see how long adults in Poland with mCRC live without their cancer getting worse (progression-free survival or PFS) when they receive fruquintinib after at least two previous treatments. Fruquintinib (TAK 113) is a medicine taken by mouth that is designed to slow tumor growth.\n\nOther aim is to find out how long adults in Poland with mCRC live while being treated with fruquintinib (overall survival or OS). The study also wants to record how fruquintinib is used in routine care in adults with mCRC in Poland (for example when treatment starts, changes in doses, and how long treatment continues). Another aim is to learn about people with mCRC, such as their medical history and past treatment as well as their quality of life while they are in the study.\n\nThe study will look at data already existing in the participants' medical charts.",[28],{"date":239,"type":40},{"date":334,"type":21},"2026-07-31",{"date":336,"type":21},"2028-03-31",{"name":338,"class":72},"Takeda",{"id":340,"slug":341,"hasResults":12,"nctId":342,"briefTitle":343,"officialTitle":344,"acronym":4,"eligibilityCriteria":345,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":346,"targetDuration":4,"studyType":22,"phases":348,"briefSummary":349,"conditions":350,"keywords":351,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":357,"lastUpdatePostDateStruct":358,"startDateStruct":360,"completionDateStruct":362,"leadSponsor":364,"locationsCount":366},"100635186","phase-3-a-study-of-precemtabart-tocentecan-with-or-without-bevacizumab-compared-to-trifluridinetipiracil-plus-bevacizumab-in-participants-with-previously-treated-metastatic-colorectal-cancer-proceade-crc-03-100635186","NCT07549412","A Study of Precemtabart Tocentecan With or Without Bevacizumab Compared to Trifluridine\u002FTipiracil Plus Bevacizumab in Participants With Previously Treated Metastatic Colorectal Cancer (PROCEADE-CRC-03)","A Randomized, Open Label, 3-arm Phase 3 Study of Precemtabart Tocentecan With or Without Bevacizumab Compared to Trifluridine\u002FTipiracil Plus Bevacizumab in Participants With Previously Treated Metastatic Colorectal Cancer (PROCEADE-CRC-03)","Inclusion Criteria:\n\n* Participants with documented histopathological diagnosis of metastatic colorectal cancer, who were intolerant to, or whose disease was refractory to, or progressed after standard systemic therapies and no more than 2 previous systemic treatment regimens in the metastatic setting.\n* Participants must have received and progressed on no more than 2 previous systemic treatment regimens in the metastatic setting\n* Eastern Cooperative Oncology Group (ECOG) performance status less than equal to 1\n* Participants must be able to swallow oral tablets, and to comply with the study requirements for all scheduled evaluations\n* Other protocol defined inclusion criteria may apply\n\nExclusion Criteria:\n\n* If Adverse Events related to previous therapies have not recovered to less than Grade 1 by National Cancer Institute - Common Terminology Criteria for Adverse Events version 6.0\n* Participant has a history of additional malignancy within 3 years before randomization\n* Participants with known brain metastases\n* Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months prior to randomization\n* Participants with ileus of more than Grade 1, or chronic inflammatory bowel disease (example ulcerative colitis, Crohn's disease) and\u002For bowel obstruction, or participants with chronic gastrointestinal disorders that, in the Investigator's opinion, might significantly interfere with proper absorption of the study treatments\n* Other protocol defined exclusion criteria may apply",{"count":347,"type":21},1020,[114],"This study aims to address the unmet medical need of participants with metastatic colorectal cancer (mCRC) who have previously been treated with irinotecan, oxaliplatin, a fluoropyrimidine, and bevacizumab, by demonstrating an overall survival prolongation with precemtabart tocentecan (Precem-TcT) as single agent or Precem-TcT in combination with bevacizumab compared to trifluoride\u002Ftipiracil (FTD-TPI) plus bevacizumab.",[28],[352,353,354,355,356],"CEACAM5","Antibody-drug conjugate","Exatecan","M9140","Precem-TcT","2026-06-15",{"date":359,"type":40},"2026-06-16",{"date":361,"type":40},"2026-05-06",{"date":363,"type":21},"2029-10-16",{"name":365,"class":72},"EMD Serono Research & Development Institute, Inc.",8,{"id":368,"slug":369,"hasResults":12,"nctId":370,"briefTitle":371,"officialTitle":372,"acronym":4,"eligibilityCriteria":373,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":374,"enrollmentInfo":375,"targetDuration":4,"studyType":22,"phases":377,"briefSummary":378,"conditions":379,"keywords":384,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":390,"lastUpdatePostDateStruct":391,"startDateStruct":393,"completionDateStruct":395,"leadSponsor":397,"locationsCount":48},"100146180","phase-2-immunotherapy-using-tumor-infiltrating-lymphocytes-for-patients-with-metastatic-cancer-100146180","NCT01174121","Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Cancer","A Phase II Study Using Short-Term Cultured, Autologous Tumor-Infiltrating Lymphocytes Following a Lymphodepleting Regimen in Metastatic Cancers Plus the Administration of Pembrolizumab","* INCLUSION CRITERIA:\n* Measurable (per RECIST v1.0 criteria), metastatic cancer of one of the following types: upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian\u002Fendometrial, or endocrine tumors including neuroendocrine tumors. Patients must have at least one lesion that is resectable for TIL generation with minimal morbidity, preferentially using minimal invasive laparoscopic or thoracoscopic surgery for removal of superficial tumor deposit.\n* Confirmation of diagnosis of metastatic cancer by the NCI Laboratory of Pathology.\n* Refractory to approved standard systemic therapy. Specifically:\n\n  * Patients with metastatic colorectal cancer must have received oxaliplatin or irinotecan.\n  * Patients with hepatocellular carcinoma must have received sorafenib (Nexavar(R)), since level 1 data support a survival benefit with this agent.\n  * Patients with breast and ovarian cancer must be refractory to both first- and second-line treatments and must have received at least one second-line chemotherapy regimen.\n* Patients with 3 or fewer brain metastases that are \\\u003C 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.\n* Age greater than or equal to 18 years and less than or equal to 72 years.\n* Clinical performance status of ECOG 0 or 1.\n* Patients of both sexes must be willing to practice birth control from the time of enrollment on this study and 12 months after the last dose of combined chemotherapy for individuals of child-bearing potential (IOCBP) and for four months after treatment for individuals that can father children.\n* IOCBP must have a negative pregnancy test be a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus.\n\nSerology\n\n* Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus may be less responsive to the experimental treatment and more susceptible to its toxicities.)\n* Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then the patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.\n\nHematology\n\n* ANC \\> 1000\u002Fmm\\^3 without the support of filgrastim\n* WBC greater than or equal to 2500\u002Fmm\\^3\n* Platelet count greater than or equal to 80,000\u002Fmm\\^3\n* Hemoglobin \\> 8.0 g\u002FdL. Subjects may be transfused to reach this cut-off.\n\nChemistry\n\n* Serum ALT\u002FAST less than or equal to 5.0 x ULN\n* Serum creatinine less than or equal to 1.5 x ULN\n* Total bilirubin less than or equal to 2.0 mg\u002FdL, except in patients with Gilbert s Syndrome, who must have a total bilirubin \\\u003C 3.0 mg\u002FdL.\n* Patients must have completed any prior systemic therapy at the time of enrollment.\n\nNote: Patients may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to less than or equal to grade 1.\n\n* Ability of subject to understand and the willingness to sign a written informed consent document.\n* Willing to sign a durable power of attorney.\n* Subjects must be co-enrolled on protocol 03-C-0277.\n\nEXCLUSION CRITERIA:\n\n* Participants who are pregnant or nursing because of the potentially dangerous effects of the treatment on the fetus or infant.\n* Concurrent systemic steroid therapy.\n* Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.\n* Advanced primary with impeding occlusion, perforation or bleeding, dependent on transfusion.\n* Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).\n* History of major organ autoimmune disease.\n* Grade 3 or 4 major organ irAEs clinically attributed to anti-PD-1\u002FPD-L1 therapy.\n* Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immunecompetence may be less responsive to the experimental treatment and more susceptible to its toxicities.)\n* History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.\n* History of coronary revascularization or ischemic symptoms.\n* For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%.\n* Documented Child-Pugh score of B or C for hepatocellular carcinoma patients with known underlying liver dysfunction.\n* For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50%.\n* Patients who are receiving any other investigational agents.","72 Years",{"count":376,"type":21},332,[25],"Background:\n\nThe NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 200 patients with melanoma. Researchers want to know if TIL shrink s tumors in people with digestive tract, urothelial, breast, or ovarian\u002Fendometrial cancers. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells.\n\nObjective:\n\nThe purpose of this study is to see if these specifically selected tumor fighting cells can cause digestive tract, urothelial, breast, or ovarian\u002Fendometrial tumors to shrink and to see if this treatment is safe.\n\nEligibility:\n\n\\- Adults age 18-72 with upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian\u002Fendometrial cancer, or glioblastoma refractory to standard chemotherapy.\n\nDesign:\n\nWork up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed.\n\nSurgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product.\n\nLeukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. (Leukapheresis is a common procedure, which removes only the white blood cells from the patient.)\n\nTreatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment.\n\nFollow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days.",[28,380,381,382,383],"Metastatic Pancreatic Cancer","Metastatic Ovarian Cancer","Metastatic Breast Carcinoma","Metastatic Endocrine Tumors\u002F Neuroendocrine Tumors",[385,386,387,388,389],"Digestive Tract Cancers","Breast Cancer","Endocrine Tumors","Ovarian\u002FEndometrial Cancer","Genitourinary Cancer","2026-06-10",{"date":392,"type":40},"2026-06-11",{"date":394,"type":40},"2010-08-26",{"date":396,"type":21},"2029-12-27",{"name":46,"class":47},{"id":399,"slug":400,"hasResults":12,"nctId":401,"briefTitle":402,"officialTitle":402,"acronym":4,"eligibilityCriteria":403,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":404,"targetDuration":4,"studyType":22,"phases":406,"briefSummary":408,"conditions":409,"keywords":4,"overallStatus":311,"whyStopped":4,"lastUpdateSubmitDate":411,"lastUpdatePostDateStruct":412,"startDateStruct":413,"completionDateStruct":414,"leadSponsor":416,"locationsCount":48},"100617420","early-phase-1-ascend-crc-profiling-and-targeting-dynamic-tumor-resistance-in-patients-with-metastatic-colorectal-cancer-100617420","NCT07318389","ASCEND-CRC: Profiling and Targeting Dynamic Tumor Resistance in Patients With Metastatic Colorectal Cancer","Eligibility Criteria\n\n* The participant has a histologically or cytologically confirmed diagnosis of colorectal cancer.\n* Confirmation of non-MSI-H\u002FpMMR status.\n* Tumor that is measurable as per RECIST v1.1 and biopsy able, defined as lesion\u002Ftumor that can be biopsied without undue risk.\n* Age ≥ 18 years.\n* ECOG performance status 0-2.\n* Due to the potential teratogenic effect of chemotherapy, 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 for an adequate amount of time following end of treatment based on the SOC indications for the administered regimen (Refer to Pregnancy Assessment Policy MD Anderson Institutional\n\nPolicy # CLN1114). This includes all female participants, between the onset of menses and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following:\n\n* Postmenopausal (no menses in greater than or equal to 12 consecutive months).\n* History of hysterectomy or bilateral salpingo-oophorectomy.\n* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).\n* History of bilateral tubal ligation or another surgical sterilization procedure.\n* Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject\u002FPartner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. 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\n  * 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 for an adequate amount of time following end of treatment based on the SOC indications for the administered regimen.\n  * The participant is willing and able to sign the informed consent in compliance with protocol requirements, including mandatory biopsies.\n\nExclusion Criteria\n\n* Pregnancy.\n* Participants with concurrent or recent (less than 1 year before consent) malignancies that have the potential to interfere with the study safety and\u002For endpoint assessments will be excluded.\n* Participants for whom there is an intent to proceed to curative therapy (i.e., resection) will be excluded.\n* Participants who have undergone treatment with both oxaliplatin and irinotecan in the metastatic setting will be excluded. Treatment with oxaliplatin in the adjuvant setting with relapse within 6 months will be counted as treatment in the metastatic setting for the purpose of this criterium.\n* For participants who have undergone treatment for metastatic disease, participants who have not progressed (clinically or radiographically) on the most recent therapy will be excluded.\n* Concurrent participation in any other interventional trial.",{"count":405,"type":21},100,[407],"EARLY_PHASE1","To find out if certain drug\u002Ftherapy combinations that are targeted to individual patients based on characteristics of their disease types may help to control the disease.",[410,28],"Dynamic Tumor Resistance","2026-06-09",{"date":392,"type":40},{"date":390,"type":21},{"date":415,"type":21},"2029-11-14",{"name":193,"class":194},{"id":418,"slug":419,"hasResults":12,"nctId":420,"briefTitle":421,"officialTitle":422,"acronym":4,"eligibilityCriteria":423,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":424,"targetDuration":4,"studyType":22,"phases":426,"briefSummary":427,"conditions":428,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":429,"lastUpdatePostDateStruct":430,"startDateStruct":431,"completionDateStruct":432,"leadSponsor":434,"locationsCount":48},"100624970","phase-1-a-study-to-investigate-cea-prit-20-in-participants-with-metastatic-colorectal-cancer-mcrc-100624970","NCT07416552","A Study to Investigate CEA-PRIT 2.0 in Participants With Metastatic Colorectal Cancer (mCRC)","A Phase I, Open-Label, Escalation and Expansion Study to Evaluate Dosimetry, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of CEA-Pre-Targeted 212Pb Therapy in Participants With Metastatic Colorectal Cancer","Inclusion Criteria:\n\n* Histologically confirmed adenocarcinoma originating from the colon or rectum\n* Metastatic disease (Stage IV American Joint Committee on Cancer, Version 7)\n* Confirmed MSS and\u002For proficient mismatch repair (MMR) status\n* Experienced disease progression during or within 3 months following the last administration of systemic anti-cancer therapies for metastatic disease\n* Presence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.\n* Life expectancy estimated by the Investigator to be \\>=12 weeks\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1\n* Adequate cardiovascular, hematological and renal function and laboratory parameters\n\nExclusion Criteria:\n\n* Pregnant or breastfeeding or intending to become pregnant\n* Participants with active central nervous system (CNS) metastases\n* History of malignancy other than the one under investigation\n* Any unresolved toxicities from prior therapy, i.e., radiotherapy, chemotherapy, targeted therapy or surgical procedure\n* Major surgery or significant traumatic injury \\\u003C4 weeks prior to the first CEA-PRIT 2.0 administration (excluding biopsies) or anticipation of the need for major surgery during study treatment\n* Participants have a known confirmed positive test for HIV\n* Positive hepatitis B surface antigen (HBsAg) test, and\u002For positive total hepatitis B core Ab (HBcAb) test at screening.\n* Positive hepatitis C (HCV) Ab test result at screening\n* Any anticancer treatment or any investigational agent within 4 weeks (or 5 times the half-life, whichever is shorter) prior to C1D1\n* Prior treatment with a CEA-targeted agent or systemic radio therapy",{"count":425,"type":21},180,[24],"This study will evaluate the dosimetry, safety, efficacy, pharmacokinetics (PK), pharmacodynamics and immunogenicity of CEA-PRIT 2.0 in participants with metastatic microsatellite-stable (MSS) mCRC who are intolerant to or have progressed after having received available standard-of-care (SOC) therapies.",[28],"2026-06-05",{"date":411,"type":40},{"date":359,"type":21},{"date":433,"type":21},"2034-02-12",{"name":218,"class":72},{"id":436,"slug":4,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":14,"acronym":4,"eligibilityCriteria":437,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":438,"targetDuration":4,"studyType":22,"phases":439,"briefSummary":26,"conditions":440,"keywords":441,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":442,"lastUpdatePostDateStruct":443,"startDateStruct":444,"completionDateStruct":445,"leadSponsor":446,"locationsCount":48},"100527570","* INCLUSION CRITERIA:\n* Participants with histologically confirmed colorectal cancer and evidence of metastatic disease.\n* Participants must have received, been ineligible to receive, or refused to receive two lines of standard systemic therapy i.e., a fluoropyrimidine with oxaliplatin or irinotecan with bevacizumab, regorafenib, trifluridine, and (if history of RAS wild-type) EGFR-targeted therapy. Participants must have received one line of systemic checkpoint inhibitor if history of advanced microsatellite instability-high \\[MSI-H\u002FdMMR\\]) metastatic colon cancer.\n* Participants who had progressive disease within 6 months before study treatment following standard adjuvant therapy are eligible if they have not received systemic therapy for metastatic disease. Participants with a history of MSI-H\u002FdMMR must have also received one line of checkpoint inhibitor therapy.\n* Age \\>= 18 years.\n* Measurable disease per RECIST 1.1.\n* ECOG performance status \\\u003C= 2.\n* Adequate organ and marrow as a function defined below:\n\n  * absolute neutrophil count (ANC) \\>= 1,500 cells\u002Fmm\\^3\n  * platelet count \\>= 100,000 cells\u002Fmm\\^3\n  * hemoglobin (Hgb) \\>= 9 g\u002FdL\n  * total bilirubin level \\\u003C 1.5 x upper limit of normal (ULN)\n  * alanine aminotransferase (ALT) \\\u003C= 2.5 x ULN OR \\\u003C= 5 x ULN for participants with liver metastases\n  * aspartate aminotransferase (AST) level \\\u003C= 2.5 x ULN OR \\\u003C= 5 x ULN for participants with liver metastases\n  * creatinine clearance (CrCl) calculated by Cockroft-Gault formula \\>= 50 mL\u002Fmin\n* Resolution of toxic effect(s) of prior anti-cancer therapy (except alopecia and neuropathy) to Grade \\\u003C=1 or to \\\u003C=2 if effective medical management of those toxicities is in place such that they are controlled per standard of care (e.g., grade 2 hypothyroidism requiring oral thyroid replacement).\n* Participants with treated brain metastases are eligible if clinically appropriate follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.\n* Participants positive for human immunodeficiency virus (HIV) are eligible if they are compliant with appropriate anti-retroviral therapy for at least 6 months, have HIV viral load \\\u003C400 copies\u002FmL, and a CD4 count \\> 350 cells\u002Fmicroliter at screening.\n* Participants positive for Hepatitis C virus (HCV) are eligible if they have completed definitive anti-viral therapy and have an undetectable viral load.\n* Individuals of child-bearing potential (IOCBP) and individuals who can father children must agree to use an effective method of contraception (barrier, hormonal, intrauterine device \\[IUD\\], surgical sterilization) at study entry and up to 6 months after the last dose of the study drug(s).\n* Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 6 months after study treatment discontinuation.\n* Participants must have lesion(s) accessible for biopsy (other than used for measurement of disease) and be willing to undergo mandatory study biopsies. Lesions to be biopsied will be determined safely accessible by the provider performing the biopsy (e.g. interventional radiology if a liver or lung biopsy) prior to performing the biopsy.\n* Participants must be able to understand and willing to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* Participants with prior investigational drug, chemotherapy, immunotherapy, or any prior therapeutic radiotherapy within 14 days prior to study treatment initiation.\n* Participants with palliative radiotherapy performed within 7 days prior to study treatment initiation.\n* Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\\> 10 mg\u002Fday of prednisone or equivalent) with the exception of:\n\n  * intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections in participants with asthma\n  * using topical, ocular, intra-articular, or intranasal corticosteroids (with minimal systemic absorption\n  * brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy).\n* Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis. Participants with chronic post-radiation pulmonary changes\u002Fscarring that is asymptomatic are eligible.\n* Active infections requiring systemic antibiotics or antifungal or antiviral treatment within 8 days prior to treatment initiation. Participants who have had appropriate antibiotics initiated but are still completing the treatment course are eligible if clinically improved or had minimal symptoms at presentation (e.g., urinary tract infection or pharyngeal streptococcal infection without evidence of systemic inflammatory response).\n\n  * History of organ transplant, including allogeneic stem cell transplantation.\n  * Participants who experienced immune-related toxicity during prior checkpoint inhibitor therapy for which permanent discontinuation of therapy was recommended (per product label or consensus guidelines) or any immune-related toxicity requiring systemic corticosteroids (with the exception of endocrinopathy that is well controlled on replacement hormones).\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs.\n* Receipt of a live vaccine within 28 days prior to treatment initiation. Note: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster (chickenpox), yellow fever, rabies, 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* History of infection with Hepatitis B virus (HBV) unless on suppressive therapy. Individuals with serologic evidence of a resolved prior HBV infection (i.e., HBsAgnegative and anti-HBc positive) are eligible.\n* Pregnancy confirmed with Beta-human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test performed in IOCBP at screening.\n* Uncontrolled intercurrent illness that would limit compliance with study requirements.",{"count":20,"type":21},[24,25],[28],[30,31,32,33,34,35],"2026-06-04",{"date":429,"type":40},{"date":42,"type":40},{"date":44,"type":21},{"name":46,"class":47},{"id":448,"slug":449,"hasResults":12,"nctId":450,"briefTitle":451,"officialTitle":452,"acronym":4,"eligibilityCriteria":453,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":454,"targetDuration":4,"studyType":329,"phases":4,"briefSummary":456,"conditions":457,"keywords":458,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":462,"lastUpdatePostDateStruct":463,"startDateStruct":465,"completionDateStruct":467,"leadSponsor":469,"locationsCount":161},"100578237","real-world-multicenter-national-study-to-evaluate-the-effectiveness-and-safety-of-biosimilar-bevacizumab-elovie-100578237","NCT06808685","Real World Multicenter National Study to Evaluate the Effectiveness and Safety of Biosimilar Bevacizumab Elovie","Real-world Multicenter National Study to Evaluate the Effectiveness and Safety of Biosimilar Bevacizumab Elovie in First-line Treatment in Participants With Unresectable Metastatic Colorectal Cancer","Inclusion Criteria:\n\n* Participants of both sexes aged 18 years or older at the start of treatment with bevacizumab;\n* Participants diagnosed with metastatic colorectal cancer, clinical stage IV, unresectable, by clinical definition in medical records, according to the investigator's assessment at the initial consultation and before any type of palliative treatment;\n* Participants who are undergoing first-line treatment with Elovie and who have completed at least 1 cycle of treatment or participants who have started first-line treatment with another bevacizumab (reference or another biosimilar other than Elovie) but who have currently switched to Elovie and completed at least 1 cycle of treatment with it, and whose data is available at the institution participating in the study;\n* Participants with the capacity to understand and consent to their participation in the study through the Free and Informed Consent Form\n\nExclusion Criteria:\n\n* Participants who use or have used bevacizumab in a manner different from that described in the current version of the Elovie® package insert;\n* Participants who have been treated with Elovie for a period longer than 12 treatment cycles;\n* Participants who have started first-line treatment with another bevacizumab (reference or another biosimilar other than Elovie) and have completed more than 2 treatment cycles with it;\n* Participants with a concomitant diagnosis of another active malignant neoplasm other than metastatic colorectal cancer.",{"count":455,"type":21},133,"Colorectal cancer is one of the most common tumors and is the second most prevalent cause of cancer death, leading to almost 1 million deaths per year.Elovie is a bevacizumab biosimilar medicine marketed by Libbs Farmacêutica, which had its registration approved by ANVISA in May 2022.At the time of registration a robust evidence package was presented that included, for example, pharmacokinetic bioequivalence studies in patients with metastatic RCC (mRCC) and a phase III study in participants with non-small cell lung cancer .Conducting a real-world study to evaluate the effectiveness and safety of bevacizumab biosimilar Elovie in patients with mCRC is crucial to provide relevant information on how this therapy behaves in real-world clinical conditions in brazilian population.",[28],[459,460,461],"Elovie","bevacizumab","metastatic colorectal cancer","2026-05-28",{"date":464,"type":40},"2026-06-01",{"date":466,"type":40},"2025-06-01",{"date":468,"type":21},"2027-11-30",{"name":470,"class":72},"Libbs Farmacêutica LTDA",{"id":472,"slug":473,"hasResults":12,"nctId":474,"briefTitle":475,"officialTitle":476,"acronym":477,"eligibilityCriteria":478,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":479,"targetDuration":4,"studyType":329,"phases":4,"briefSummary":481,"conditions":482,"keywords":484,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":499,"lastUpdatePostDateStruct":500,"startDateStruct":501,"completionDateStruct":503,"leadSponsor":505,"locationsCount":229},"100637435","primary-and-acquired-resistance-to-targeted-treatment-in-braf-v600e-mutated-metastatic-colorectal-cancer-100637435","NCT07617610","Primary and Acquired Resistance to Targeted Treatment in BRAF V600E-mutated Metastatic Colorectal Cancer","Primary and Acquired Resistance to Targeted Treatment in BRAF V600E-mutated Metastatic Colorectal Cancer (PARTACER-Suisse)","PARTACER","Inclusion Criteria:\n\n* Diagnosis of unresectable or metastatic BRAF V600E-mutated colorectal cancer\n* Planned initiation of treatment with combined anti-EGFR antibody and BRAF inhibitor\n* Patients receiving treatment in any line, with or without chemotherapy\n* At least one tumor lesion accessible for biopsy\n* ECOG performance status 0-2\n* Life expectancy of at least 3 months\n* Age ≥18 years\n* Ability to provide written informed consent\n\nExclusion Criteria:\n\n* Medical or surgical contraindication for tumor biopsy\n* Active second malignancy (except non-melanoma skin cancer)\n* Inability to comply with study procedures (e.g., due to language barriers or cognitive impairment)\n* Pregnancy or breastfeeding\n* Previous treatment with a BRAF inhibitor",{"count":480,"type":21},30,"This study prospectively investigates the molecular mechanisms of primary and acquired resistance to standard-of-care BRAF V600E-directed therapy in patients with metastatic colorectal cancer and aims to pre-clinically develop novel strategies to reverse therapy resistance. Clinically approved combination treatment with cetuximab, encorafenib and chemotherapy improves patient outcomes, yet patients eventually experience disease progression. In this prospective multicenter study, tumor tissue, blood, and stool samples will be collected before treatment and at progression, to identify genetic and non-genetic mechanisms of resistance. Additionally, tumor tissue-based in vitro models (patient-derived organoids, PDOs) will be generated and exploited for functional in vitro testing, including genomic and pharmacologic perturbation studies. The overarching goal is to generate knowledge that can help develop new and more effective treatment strategies for future patients.",[28,483],"BRAF V600E Mutation",[28,236,485,486,487,488,489,490,491,492,493,494,495,496,497,498],"BRAF V600E","Targeted therapy resistance","Encorafenib","Cetuximab","EGFR inhibition","BRAF inhibition","Liquid biopsy","Precision oncology","Patient-derived organoids","Circulating tumor DNA","ctDNA","Microbiome","Comprehensive genomic profiling","SCI\u002FSAKK","2026-05-22",{"date":464,"type":40},{"date":502,"type":40},"2025-05-25",{"date":504,"type":21},"2030-09",{"name":506,"class":194},"Swiss Cancer Institute",{"id":508,"slug":509,"hasResults":12,"nctId":510,"briefTitle":511,"officialTitle":512,"acronym":513,"eligibilityCriteria":514,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":515,"targetDuration":4,"studyType":22,"phases":517,"briefSummary":518,"conditions":519,"keywords":520,"overallStatus":311,"whyStopped":4,"lastUpdateSubmitDate":524,"lastUpdatePostDateStruct":525,"startDateStruct":527,"completionDateStruct":528,"leadSponsor":530,"locationsCount":532},"100620579","phase-2-testing-ivonescimab-in-combination-with-chemotherapy-in-patients-with-metastatic-colorectal-cancers-without-liver-metastases-100620579","NCT07359456","Testing Ivonescimab in Combination With Chemotherapy in Patients With Metastatic Colorectal Cancers Without Liver Metastases","Randomized Phase 2 Study of Second-line Chemotherapy Comparing FOLFIRI + Ivonescimab Versus FOLFIRI + Bevacizumab in Microsatellite Stable (MSS)\u002F Proficient MisMatch Repair (pMMR) BRAF Wild Type (BRAFwt) Advanced Colorectal Cancer (mCRC) Without Liver Metastases","COLIBRI-GI","Inclusion Criteria:\n\n1. Signed a written informed consent form prior to any trial specific procedures. Note: If the patient is physically unable to provide their written consent, a trusted person of their choice, independent of the Investigator or the Sponsor, can confirm the patients consent in writing.\n2. Histologically confirmed diagnosis of non resectable pMMR (by IHC) and MSS (by molecular biology) and BRAFwt metastatic colorectal cancer with no liver metastasis.\n3. Must have previously received 1st-line treatment with FOLFOX +\u002F- anti-VEGF (Vascular endothelial growth factor) or EGFR (Epithelial Growth Factor Receptor) therapy (including recurrence within 6 months after adjuvant FOLFOX for localized CRC and adjuvant\u002Fperioperative FOLFOX for mCRC, as well as progressive disease under maintenance treatment for mCRC) OR 1st-line treatment with FOLFIRINOX (Oxaliplatin, Irinotecan, 5FU, Folinic acid) (under the following condition: no progression under triplet-chemotherapy, progression under LV5FU2 (Folinic acid + 5FU) maintenance, irinotecan stopped for at least 3 months for a reason other than progression)\n4. Presence of at least one measurable lesion as assessed by the investigator according to RECIST v1.1.\n5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n6. Age ≥18 years.\n7. Adequate Organ Function:\n\n   * Hematology (no blood transfusions or growth factor therapy used within 7 days of the screening):\n\n     * Absolute neutrophil count (ANC) ≥ 1.5 × 109\u002FL\n     * Platelet count ≥ 100 × 109\u002FL\n     * Hemoglobin ≥ 10.0 g\u002FdL\n   * Kidneys:\n\n     * Creatinine clearance ≥ 50 mL\u002Fmin using the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) value ≥50 mL\u002Fmin using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation\n     * Urine protein \\\u003C 2+ or 24 hour urine protein quantification \\\u003C 1.0 g\n   * Liver:\n\n     * Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN)\n     * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN\n   * Coagulation: prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 x ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy, or prophylactic coagulation)\n8. Life expectancy ≥ 3 months\n9. Women of childbearing potential (WOCBP) having sex with an unsterilized male partner and unsterilized males having sex with a female partner of childbearing potential, must agree to use an effective method of contraception for the duration of trial participation and as required after completing study treatment (9 months after the last dose of trial treatment). Men must also agree to not donate sperm and women must agree to not donate oocytes during the specified period.\n10. WOCBP must have a negative serum pregnancy test performed within 3 days before inclusion and a negative urine pregnancy test on the day of first dose, prior to treatment administration.\n11. Willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests, and other study procedures\n12. Affiliation to the Social Security System (or equivalent)\n\nExclusion Criteria:\n\n1. Presence of liver metastases by CT-scan or MRI. Note: Patients with prior definitively treated liver metastases (surgical resection, microwave or radiofrequency ablation, or stereotactic body radiation therapy) are eligible if no evidence of metastatic disease in the liver on subsequent imaging).\n2. History of Gilbert's syndrome\n3. Other current or previous malignancy within the past 3 years (with the exception of squamous cell carcinoma of the skin or in situ tumour treated by surgery).\n4. Patients with high microsatellite instability (MSI-H), mismatched repair disease (dMMR) and\u002For BRAF V600E mutated tumor.\n5. Toxicities from previous treatment not resolved to grade ≤ 1 (according to the version 5.0 of the National Cancer Institute - Common terminology criteria for adverse events \\[NCI-CTCAE v5.0\\]) before treatment start with the exception of alopecia.\n6. Major surgical procedures or serious trauma within 4 weeks prior to randomization, 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 randomization.\n7. History of bleeding tendencies or coagulopathy and\u002For clinically significant bleeding symptoms or risk within 4 weeks prior to randomization, including but not limited to:\n\n   * Clinically significant GI bleeding such as hematochezia or any episodes of melena or documented acute hemoglobin drop of more than 1 gm in 2 weeks prior to randomization\n   * Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to randomization is not allowed. The use of full-dose anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits according to the medical standard of the enrolling institution.\n8. Current hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy\n9. History of major diseases before randomization, specifically:\n\n   * Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association (NYHA) classification ≥ grade 2) or vascular disease (eg, aortic aneurysm at risk of rupture) that required hospitalization within 12 months prior to randomization, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)\n   * History of oesophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before randomization\n   * History of arterial thromboembolic event, venous thromboembolic event of Grade 3 and above 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 6 months prior to randomization\n   * Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before randomization\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 randomization\n10. Current presence of significant radiographic or clinical manifestations of gastrointestinal (GI) obstruction.\n11. Ascites requiring paracentesis within last 30 days\n12. Symptomatic central nervous system (CNS) metastases or leptomeningeal disease Note: Asymptomatic patients (previously treated or untreated) in the absence of corticosteroid and anti-epileptic therapy are allowed. CNS metastases must be stable for ≥4 weeks prior to randomization.\n13. Presence of brainstem, meningeal metastases, spinal cord metastases, or compression.\n14. Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)\n15. Prior immunosuppressive therapy: immunosuppressive doses of systemic medications of \\> 10 mg\u002Fday of prednisone or equivalent must be discontinued ≥ 2 weeks before the first dose of study treatment. Short courses of high dose corticosteroids and\u002For continuous low dose of prednisone (\\\u003C 10 mg\u002Fday) are permitted. In addition, inhaled, intranasal, intraocular, and\u002For joint injections of corticosteroids are allowed.\n16. Any prior clinically significant or active autoimmune disease requiring systemic therapy (eg, with disease- modifying drugs, prednisone \\>10 mg daily or equivalent, immunosuppressant therapy or immunomodulatory agents \\[eg, infliximab or IVIG (intravenous immunoglobulin)\\]) within 2 years prior to randomization; however, the following will be allowed:\n\n    o Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.\n17. Known history of, or any evidence of, interstitial lung disease.\n18. Patient with non-controlled human immunodeficiency virus (HIV) (positive HIV 1\u002F2 antibodies) infection (patient with undetectable viral load (HIV RNA PCR) and CD4 (T CD4 lymphocytes) above 350 either spontaneously or on stable anti-viral regimen).\n19. Known human immunodeficiency virus infection with CD4+ T cell counts \\\u003C 350 cells\u002FµL, hepatitis C infection (subjects with hepatitis C who achieve a sustained virologic response following antiviral therapy are permitted), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody who achieve sustained virologic response with antiviral therapy directed at hepatitis B are permitted)\n20. Proven complete deficiency of dihydropyrimidine dehydrogenase (DPD).\n21. Known history of hypersensitivity to ivonescimab and to one of the study drugs or one of its excipients\n22. Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.\n23. Pregnant or breast-feeding females.\n24. Participation in another therapeutic trial within the 30 days prior to entering the study. Participation in an observational trial would be acceptable.\n25. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.\n26. Individuals deprived of liberty or placed under protective custody or guardianship.",{"count":516,"type":21},130,[25],"The goal of this clinical trial is to evaluate the superiority of ivonescimab combined with FOLFIRI over FOLFIRI + bevacizumab as second-line treatment of non resectable pMMR\u002FMSS BRAFwt mCRC patients without liver metastases in terms of PFS. The main questions it aims to answer are:\n\nDoes FOLFIRI + ivonescimab improve progression-free survival compared to FOLFIRI + bevacizumab?\n\nParticipants will:\n\nTake FOLFIRI + ivonescimab or FOLFIRI + bevacizumab every 2 weeks for a maximum of 24 months Visit the clinic once every 2 weeks for checkups and tests, and have imaging done every 8 weeks Complete some quality of life questionnaires every 8 weeks",[28],[521,522,523],"Metastatic colorectal cancer","ivonescimab","BRAF wild-type","2026-05-18",{"date":526,"type":40},"2026-05-19",{"date":315,"type":21},{"date":529,"type":21},"2033-08",{"name":531,"class":194},"UNICANCER",22,{"id":534,"slug":535,"hasResults":12,"nctId":536,"briefTitle":537,"officialTitle":537,"acronym":4,"eligibilityCriteria":538,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":539,"targetDuration":4,"studyType":22,"phases":541,"briefSummary":542,"conditions":543,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":524,"lastUpdatePostDateStruct":544,"startDateStruct":546,"completionDateStruct":548,"leadSponsor":550,"locationsCount":48},"100589833","phase-2-phase-ii-study-of-anti-pd-1vegf-bispecific-antibody-ivonescimab-in-patients-with-previously-treated-metastatic-colorectal-cancer-100589833","NCT06959550","Phase II Study of Anti-PD-1\u002FVEGF Bispecific Antibody Ivonescimab in Patients With Previously Treated Metastatic Colorectal Cancer","Inclusion Criteria:\n\n1. Capable of giving signed informed consent\n2. Male and female adult participants 18 years of age or older on day of signing informed consent.\n3. Histological or cytological confirmed advanced, metastatic adenocarcinoma of colon or rectum.\n4. Known MMR or MSI status performed by local standard of practice. (e.g., IHC and\u002For PCR, next-generation sequencing)\n5. Cohort-specific criteria\n\n   * Cohort 1: MSI-H\u002FdMMR: ICI-refractory\n\n     * dMMR or MSI-H per local testing\n     * Demonstrated radiographic or clinical disease progression following treatment with immune checkpoint inhibitors including anti-PD-1 +\u002F- anti-CTLA-4 therapy. If progression occurred after first imaging assessment, then pseudo-progression should be excluded by concurrent carcinoembryonic antigen (CEA) or other tumor marker or ctDNA elevation, or clinical symptom progression, or short-interval repeat imaging confirming progression.\n     * Must have received at least 2 doses of a PD1\u002FPD-L1 inhibitor.\n     * Progressive disease either during therapy or within 3 months of last dose of therapy.\n     * No serious adverse immune-related adverse events (grade 3 or higher) with previous immune checkpoint therapy, that were symptomatic and required prolonged immunosuppression (\\>6 weeks).\n   * Cohort 2: pMMR with liver metastases\n\n     * pMMR or non-MSI-H per local testing\n     * Presence of active liver metastases per radiographic imaging\n     * Patients with any bulky liver metastases measuring \\>5.0 cm are not eligible\n   * Cohort 3: pMMR without liver metastases\n\n     * pMMR or non-MSI-H per local testing\n     * No liver metastases per radiographic imaging (note: previously treated or resected liver metastases are allowed if treatment was \\>6 months prior without liver progression)\n6. Known extended RAS and BRAF status as per local standard of practice (Cohorts 2 and 3 only)\n7. Participant must have progressed (radiologically or clinically) or been intolerant to fluoropyrimidine, irinotecan, and oxaliplatin (Cohorts 2 and 3 only)\n\n   * Patient must have evidence of progression on or after the last treatment regimen received and within 6 months prior to study enrollment\n   * Patients who were intolerant to prior systemic chemotherapy regimens are eligible if there is documented evidence of clinically significant intolerance despite adequate supportive measures.\n   * Perioperative chemotherapy exposure can be considered if the participant had disease recurrence within 12 months of completion of neoadjuvant chemotherapy or 6 months of completion of adjuvant chemotherapy\n8. ECOG (Eastern Cooperative Oncology Group) PS of 0 to 1.\n9. Adequate hematologic and organ function as assessed by the following laboratory tests performed within 7 days before treatment initiation:\n\n   * Total bilirubin .1.5 x the upper limit of normal (ULN). Total bilirubin (.3 x ULN) is allowed if Gilbert fs syndrome is documented.\n   * Alanine transaminase (ALT) and aspartate aminotransferase (AST) .2.5x ULN (.5 x ULN for patients with liver involvement of their cancer)\n   * Platelet count .100,000 \u002Fmm3, Hemoglobin (Hb) .9 g\u002FdL, WBC .2000\u002FƒÊL absolute neutrophil count (ANC) .1500\u002Fmm3 without red blood cell transfusion or growth factor administered within 7 days of screening CBC.\n   * Serum creatinine .1.5 x ULN or creatinine clearance .50 mL\u002Fmin (measured or calculated using the Cockroft-Gault formula)\n   * Prothrombin time-international normalized ratio (PT\u002FINR) . 1.5 x ULN and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) . 1.5 \\~ 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   * Estimated CrCl . 50 mL\u002Fmin.\n   * Proteinuria . 30 mg\u002FdL.\n10. Measurable disease as determined by iRECIST v1.1.\n11. Ability to provide recent tumor tissue is mandatory for all participants at screening, either through pre-treatment biopsy or archived tissue. For archived tissue, FFPE block or a minimum of 10 slides is recommended with exceptions to these criteria permitted for consideration by the principal investigator.\n12. Anticipated life expectancy greater than 3 months\n13. Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of study intervention and 4 months after the last dose of study drug. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study intervention and 4 months after the last dose of study drug. In addition, male participants must be willing to refrain from sperm donation during this time. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.\n\nExclusion Criteria:\n\n1. Any single liver metastasis \\>5.0 cm (Cohort 2 only)\n2. Except for MSI-H\u002FdMMR tumors, prior therapy with PD-1, PD-L1, or CTLA-4 inhibitors (Cohorts 2 and 3 only).\n3. Patient who discontinued prior therapy with immune checkpoint inhibitors due to Grade 2 neurologic, cardiac, or ophthalmologic events or recurrent Grade 2 pneumonitis are not eligible for the trial (Cohort 1 only).\n4. Systemic anti-cancer treatment within 14 days or less than 5 half-lives (whichever is shorter) of the first dose of study treatment.\n5. Has unresolved clinically significant toxicity of greater than or equal to NCI Institute Common Terminology Criteria for AEs (CTCAE v5.0) grade 2 attributed to any prior therapies (excluding anemia, lymphopenia, alopecia, skin pigmentation, and immune toxicities for MSI-H\u002FdMMR ICI-refractory cohort as listed in cohort inclusion criteria).\n6. History of arterial thromboembolic event, venous thromboembolic event of grade 3 and above as specified in NCI CTCAE v5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to enrollment\n7. 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 randomization, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)\n8. Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before enrollment\n9. Poorly controlled hypertension with repeated systolic blood pressure . 150 mmHg or diastolic blood pressure . 100 mmHg after oral antihypertensive therapy\n10. 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 randomization, however the following will be allowed: a. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted. b. Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted\n11. Know history of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominopelvic fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months prior to enrollment\n12. History of perforation of the gastrointestinal tract and\u002For fistula, gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), or extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to enrollment\n13. History of bleeding tendencies or coagulopathy and\u002For clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment, 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 enrollment is not permitted. The use of full-dose anticoagulants is permitted if the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution.\n14. Subjects whose tumors invade peripheral important organs and blood vessels (such as heart and pericardium, trachea, esophagus, aorta, superior vena cava, etc), and who are at risk of esophageal tracheal fistula or esophageal pleural fistula or intestinal fistula\n15. Symptomatic 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. Note: Patients must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone .10 mg daily or equivalent).\n16. Live vaccine or live attenuated vaccine within 4 weeks prior to planned enrollment, or if scheduled to receive a live vaccine or live attenuated vaccine during the study period. Inactivated vaccines are permitted.\n17. 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. Participants with HIV, HCV, or HBV infection may be included if suppressive antiviral therapy has been administered and the viral load is undetectable.\n18. Has pre-existing peripheral neuropathy that is . grade 2 per NCI CTCAE v5.0.\n19. Major surgical procedures or serious trauma within 4 weeks prior to enrollment, 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 enrollment.\n20. Uncontrolled pleural effusions, pericardial effusions, or ascites that is clinically symptomatic. Note: Patients managed with indwelling catheters (e.g. PleurX) are allowed.\n21. History of non-infectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease\n22. Active or prior history of inflammatory bowel disease (eg, Crohn fs disease, ulcerative colitis, or chronic diarrhea)\n23. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation\n24. Known allergy to any component of any study drug or known history of severe hypersensitivity to other monoclonal antibodies\n25. Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results, in the opinion of the investigator.\n26. Participants with a condition requiring systemic treatment with either corticosteroids (\\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \\>10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.\n27. Pregnancy or breast feeding.\n28. Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule.",{"count":540,"type":21},90,[25],"The goal of this clinical research study is to learn if ivonescimab can help to control previously treated, metastatic colorectal cancer.",[28],{"date":545,"type":40},"2026-05-20",{"date":547,"type":40},"2025-07-28",{"date":549,"type":21},"2030-07-01",{"name":193,"class":194},{"id":552,"slug":553,"hasResults":12,"nctId":554,"briefTitle":555,"officialTitle":556,"acronym":557,"eligibilityCriteria":558,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":559,"targetDuration":4,"studyType":22,"phases":561,"briefSummary":562,"conditions":563,"keywords":565,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":567,"lastUpdatePostDateStruct":568,"startDateStruct":569,"completionDateStruct":571,"leadSponsor":573,"locationsCount":575},"100579420","phase-2-evaluation-of-rbs2418-in-patients-with-advanced-metastatic-and-progressive-colorectal-cancer-100579420","NCT06824064","Evaluation of RBS2418 in Patients With Advanced, Metastatic, and Progressive Colorectal Cancer","A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study of RBS2418 Plus Best Supportive Care (BSC) in Subjects With Advanced, Metastatic, and Progressive Colorectal Cancer","VISTA-1","Inclusion Criteria:\n\n1. At least 18 years of age on the day of signing informed consent.\n2. Male and female subjects with advanced, metastatic, progressive CRC who have received, been ineligible for, intolerant to, or declined all approved standard of care (SOC) therapies for metastatic CRC, as per local SOC treatment regimens. Additionally, subjects must have documented PD based on two scans performed within 2 to 4 months of study initiation.\n3. Have histologically or cytologically confirmed CRC diagnosis based on pathology report.\n4. Willing to submit a pre-treatment tissue sample (archival, or fresh tissue if archival is not available).\n\nExclusion Criteria:\n\n1. Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy, systemic immunotherapy, or radiation therapy within 2 weeks prior to the first dose of study treatment; or if subject has not recovered (i.e., ≤ to Grade 1 or returned to baseline level) from AEs due to a previously administered agent; the following exceptions are allowed:\n\n   * Palliative radiotherapy for bone metastases or soft tissue lesions should be completed \\>7 days prior to the first dose of study treatment.\n   * Hormone-replacement therapy or oral contraceptives.\n   * Subjects with Grade 2 neuropathy or Grade 2 alopecia.\n2. Subjects with evidence of rapid progression on prior therapy resulting in rapid clinical deterioration.\n3. Malignancies other than indications open for enrollment within 3 years prior to Day 1, except for those with negligible risk of metastasis or death treated with expected curative outcome, undergoing active surveillance, or treatment-naïve for indolent tumors.",{"count":560,"type":21},150,[25],"RBS2418 is a specific immune modulator that works through the inhibition of ectonucleotide pyrophosphatase\u002Fphosphodiesterase 1 (ENPP1) and is designed to lead to anti-tumor immunity by protecting endogenous 2'-3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from hydrolysis and leading to the activation of antigen-presenting cells followed by T cell activation. The hypothesis is that RBS2418 versus placebo will be generally safe, well-tolerated, immunogenic, and will lead to anti-tumor responses in adult subjects for the treatment of advanced, metastatic, and progressive colorectal cancer (CRC).",[28,564],"Advanced Colorectal Cancer",[566],"Advanced, Metastatic, Progressive Colorectal Cancer","2026-05-15",{"date":524,"type":40},{"date":570,"type":40},"2025-01-17",{"date":572,"type":21},"2027-12",{"name":574,"class":72},"Riboscience, LLC.",5,{"id":577,"slug":578,"hasResults":12,"nctId":579,"briefTitle":580,"officialTitle":580,"acronym":581,"eligibilityCriteria":582,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":583,"targetDuration":4,"studyType":22,"phases":585,"briefSummary":587,"conditions":588,"keywords":590,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":594,"lastUpdatePostDateStruct":595,"startDateStruct":597,"completionDateStruct":599,"leadSponsor":601,"locationsCount":48},"100530771","fapi-molecular-imaging-for-diagnosis-of-the-cms4-unfavorable-colorectal-cancer-subtype-100530771","NCT06191120","FAPI Molecular Imaging for Diagnosis of the CMS4 Unfavorable Colorectal Cancer Subtype","FoCus","Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Candidates for liver metastatectomy at the time of liver metastasis diagnosis as clinically indicated in the tumor board (RAKU).\n* Patients must have given written informed consent.\n* At least one liver metastasis should have a longest diameter of a least 1.5 cm as measured on routinely performed imaging (e.g. magnetic resonance imaging, CT-scan or ultrasound). This minimum diameter will guarantee sufficient tissue material for analysis and will prevent underestimation of \\[18F\\]-ALF-FAPI-74 uptake due to partial volume effects.\n* CRC patients who received prior treatment before clinical indication for surgical liver metastases resection (both synchronous and metachronous patients, as well as a re-resection of liver metastatic disease) are allowed to enter the study. This is because our prime interest is in the relation between FAPI uptake and the presence of CMS4 at the same point in time, which will likely not be biased by earlier therapies.\n* It is allowed for patients to receive concurrent radiofrequency ablation or other local treatments directed to other metastatic disease locations, if at least one liver metastasis of sufficient size is planned to be surgically removed and therefore available for tissue analysis.\n* It is allowed for patients to be treated with pre-surgical radiotherapy directed to the primary tumor (e.g. in rectal cancer patients).\n\nExclusion Criteria:\n\n* Pregnancy.\n* Patients treated with a pre-surgical chemotherapy regimen that does not include a fluoropyrimidine.",{"count":584,"type":21},45,[586],"NA","Colorectal cancer (CRC) is the 3rd most common cancer worldwide and accounts for \\~14,000 new diagnoses and \\~5,000 deaths in the Netherlands yearly (1.9 million and 935 thousand on a global level). Large scale transcriptional profiling of primary CRC tumors has revealed the presence of four distinct consensus molecular subtypes (CMSs). The CMS4 subtype is associated with a poor prognosis, especially in early CRC, and may benefit less from several standard systemic treatments (e.g. oxaliplatin, 5-fluorouracil, cetuximab), while being relatively sensitive to irinotecan. This is relevant as in the metastatic setting often the first choice first-line systemic therapy regimen is oxaliplatin and not irinotecan-based. Furthermore, tumor cells can acquire a CMS4 phenotype following exposure to chemotherapy, which may contribute to therapy resistance.\n\nCMS4 accounts for \\~25% of all early-stage CRC patients and is more prevalent in advanced disease stages (\\~40% in stage IV CRC). Currently available CMS4 diagnostic tests require tumor tissue samples. The interpretation of biopsy-based CMS4 diagnosis is however complicated by large intra- and inter-lesion heterogeneity of CMS4 status. Extensive biopsy protocols could address the problem of CMS4 heterogeneity but are challenging in routine clinical practice. The development of CMS4-targeted therapy strategies therefore requires a more robust and clinically applicable diagnostic test for comprehensive quantitative assessment of CMS4 status of all lesions - primary and metastatic - in individual cancer patients.\n\nA promising solution for such a diagnostic test is to use a radiotracer that enables the quantitative assessment of CMS4 in vivo by whole body molecular imaging. This technique is particularly suited to assess biomarkers with heterogeneous expression: for diagnostic purposes, as a companion diagnostic for (targeted) therapies, or as part of a 'theranostic' strategy where patient selection using the diagnostic radiotracer is followed by treatment with the same tracer labeled to a therapeutic compound.\n\nRadiolabeled fibroblast activating protein inhibitor (FAPI) is an emerging diagnostic radiotracer that allows the comprehensive whole-body, whole-tumor assessment of fibroblast activation protein (FAP) expression in humans with a very low background uptake also at frequent CRC metastatic sites including the liver. FAP is an excellent candidate molecular imaging target for CMS4, as it is highly expressed on cancer-associated fibroblasts (CAF) that are abundantly present in this CRC subtype. Indeed, the investigators found that FAP gene-expression measured in tumor biopsies - as a single marker - accurately discriminates CMS4 from other CRC subtypes (area under the receiver operating characteristic curve (AUROC): 0.91; 95% confidence interval (CI): 0.90-0.93). The FoCus study will aim to take a next step by relating in vivo assessed FAP protein-expression by \\[18F\\]-ALF-FAPI-74 positron emission tomography (PET) \u002F computed tomography (CT) to CMS4 status in patients eligible for colorectal liver metastatectomy as a first proof of concept. Ultimately this will contribute to the development of a diagnostic tool for the comprehensive assessment of CMS4 load in patients with (metastatic) CRC by using \\[18F\\]-ALF-FAPI-74 PET\u002FCT molecular imaging, to guide CMS4 subtype-directed therapy decisions.",[28,589],"Metastatic Cancer to Liver",[591,592,593],"CMS4","FAPI","Imaging","2026-05-12",{"date":596,"type":40},"2026-05-14",{"date":598,"type":40},"2024-08-05",{"date":600,"type":21},"2031-07",{"name":602,"class":194},"UMC Utrecht",{"id":604,"slug":4,"hasResults":12,"nctId":77,"briefTitle":78,"officialTitle":79,"acronym":80,"eligibilityCriteria":81,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":82,"enrollmentInfo":605,"targetDuration":4,"studyType":22,"phases":607,"briefSummary":86,"conditions":608,"keywords":609,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":610,"lastUpdatePostDateStruct":611,"startDateStruct":613,"completionDateStruct":614,"leadSponsor":616,"locationsCount":102},"100577007",{"count":606,"type":21},120,[25],[28],[89,90,91,92,93,94,80],"2026-05-08",{"date":612,"type":40},"2026-05-11",{"date":97,"type":40},{"date":615,"type":21},"2028-06-07",{"name":101,"class":72},{"id":618,"slug":619,"hasResults":12,"nctId":620,"briefTitle":621,"officialTitle":622,"acronym":4,"eligibilityCriteria":623,"healthyVolunteers":12,"sex":16,"minAge":17,"maxAge":624,"enrollmentInfo":625,"targetDuration":4,"studyType":22,"phases":626,"briefSummary":627,"conditions":628,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":629,"lastUpdatePostDateStruct":630,"startDateStruct":632,"completionDateStruct":634,"leadSponsor":636,"locationsCount":48},"100631674","phase-2-js212-combination-therapies-in-metastatic-colorectal-cancer-100631674","NCT07503756","JS212 Combination Therapies in Metastatic Colorectal Cancer","An Open-label, Multicenter Phase 2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of JS212 Combination Therapies in Patients With Metastatic Colorectal Cancer","Inclusion Criteria:\n\n* 1Participants must meet the following key criteria\n* Adults aged 18-75 years with histologically confirmed metastatic colorectal adenocarcinoma\n* Microsatellite stable (MSS) or mismatch repair proficient (pMMR) disease\n* No prior systemic therapy for advanced or metastatic disease\n* At least one measurable lesion according to RECIST v1.1\n* ECOG performance status 0-1\n* Adequate hematologic, hepatic, renal, and coagulation function\n* Life expectancy ≥12 weeks\n* Willingness to provide tumor tissue samples for biomarker analyses\n* Ability to provide written informed consent\n\nExclusion Criteria:\n\n* Participants meeting any of the following criteria will be excluded\n* Prior treatment with EGFR- or HER3-targeted antibody-drug conjugates or topoisomerase I inhibitor-based ADCs\n* Recent major surgery, radiotherapy, or systemic anticancer therapy prior to study treatment\n* Active or uncontrolled infections or significant cardiovascular disease\n* Known active central nervous system metastases\n* History of autoimmune disease requiring systemic therapy\n* Significant bleeding disorders or high risk of hemorrhage\n* Active viral infections such as uncontrolled hepatitis B, hepatitis C, or HIV\n* Any other serious medical or psychiatric condition that may interfere with study participation","75 Years",{"count":84,"type":21},[25],"This is an open-label, multicenter Phase 2 clinical study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of JS212-based combination therapies in patients with metastatic colorectal cancer (mCRC).\n\nJS212 is a bispecific antibody-drug conjugate (ADC) targeting epidermal growth factor receptor (EGFR) and HER3 with a topoisomerase I inhibitor payload. Preclinical and early clinical data suggest that dual targeting of EGFR and HER3 may enhance antitumor activity and overcome resistance mechanisms associated with EGFR- or HER2-directed therapies.\n\nThis study will investigate JS212 in combination with capecitabine, with or without Bevacizumab, and JS212 in combination with chemotherapy (XELOX: capecitabine and oxaliplatin), with or without the PD-1\u002FVEGF bispecific antibody JS207, in patients with mCRC.\n\nThe study will assess safety, determine the recommended Phase 3 dose (RP3D), and evaluate preliminary antitumor activity of the combination regimens.",[28],"2026-04-29",{"date":631,"type":40},"2026-05-05",{"date":633,"type":40},"2026-04-25",{"date":635,"type":21},"2028-03-30",{"name":637,"class":194},"Shanghai Junshi Bioscience Co., Ltd."]