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Participants will also receive I-DXd up to 12 mg\u002Fkg via IV infusion Q3W, until PD or toxicity; 5-FU 400 mg\u002Fm\\^2 bolus IV infusion followed by 2400 mg\u002Fm\\^2 continuous 46-48 hour IV infusion Q2W, OR 2400 mg\u002Fm\\^2 continuous 46-48 hour IV infusion Q2W, until PD or toxicity; and leucovorin 400 mg\u002Fm\\^2 OR levoleucovorin 200 mg\u002Fm\\^2 via IV infusion Q2W, until PD or toxicity.",[13,23,14,15,16,24],{"label":30,"type":20,"description":31,"interventionNames":32},"Pembrolizumab + I-DXd + 5-FU IV + Leucovorin or Levoleucovorin + Oxaliplatin","Participants will receive 200 mg of pembrolizumab via IV infusion Q3W on Day 1 of each 21-day cycle up to 35 cycles (up to approximately 2 years). Participants will also receive up to 12 mg\u002Fkg I-DXd via IV infusion q3w, until PD or toxicity; 5-FU 2400 mg\u002Fm\\^2 continuous 46-48 hour IV infusion Q2W, until PD or toxicity; 60mg\u002Fm\\^2 oxaliplatin via IV infusion Q2W, until PD or toxicity; and leucovorin 400 mg\u002Fm\\^2 OR levoleucovorin 200 mg\u002Fm\\^2 via IV infusion Q2W, until PD or toxicity.",[13,23,14,15,16,17,24],{"label":34,"type":20,"description":35,"interventionNames":36},"Pembrolizumab + Sacituzumab tirumotecan + 5-FU IV + Leucovorin or Levoleucovorin","Participants will receive 400 mg pembrolizumab via IV infusion Q6W on Day 1 of each 42-day cycle up to 18 cycles (up to approximately 2 years). 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( Site 1701)","Geneva","1211",{"type":99,"coordinates":529},[530,531],6.14569,46.20222,{"lat":531,"lon":530},[534],{"name":106,"role":86,"phone":535,"phoneExt":58,"email":58},"+41 (0)22 372 95 77",{"facility":537,"status":92,"city":538,"state":539,"zip":540,"country":541,"countryCode":542,"cosmosGeoPoint":58,"geoPoint":58,"contacts":543},"Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 1009)","Kaoshiung","Kaohsiung","807","Taiwan","TW",[544],{"name":106,"role":86,"phone":545,"phoneExt":58,"email":58},"+8867-3121101#7451",{"facility":547,"status":92,"city":548,"state":58,"zip":549,"country":541,"countryCode":542,"cosmosGeoPoint":550,"geoPoint":554,"contacts":555},"Kaohsiung Chang Gung Memorial Hospital ( Site 1003)","Kaohsiung City","83301",{"type":99,"coordinates":551},[552,553],120.31333,22.61626,{"lat":553,"lon":552},[556],{"name":106,"role":86,"phone":557,"phoneExt":58,"email":58},"+88677317123x3679",{"facility":559,"status":92,"city":560,"state":58,"zip":561,"country":541,"countryCode":542,"cosmosGeoPoint":562,"geoPoint":566,"contacts":567},"China Medical University Hospital ( Site 1007)","Taichung","40707",{"type":99,"coordinates":563},[564,565],120.6839,24.1469,{"lat":565,"lon":564},[568],{"name":106,"role":86,"phone":569,"phoneExt":58,"email":58},"886-4-22052121",{"facility":571,"status":92,"city":572,"state":58,"zip":573,"country":541,"countryCode":542,"cosmosGeoPoint":574,"geoPoint":578,"contacts":579},"National Cheng Kung University Hospital ( Site 1001)","Tainan","704",{"type":99,"coordinates":575},[576,577],120.21333,22.99083,{"lat":577,"lon":576},[580],{"name":106,"role":86,"phone":581,"phoneExt":58,"email":58},"+88662353535x4559",{"facility":583,"status":92,"city":584,"state":58,"zip":585,"country":541,"countryCode":542,"cosmosGeoPoint":586,"geoPoint":590,"contacts":591},"National Taiwan University Hospital ( Site 1000)","Taipei","100225",{"type":99,"coordinates":587},[588,589],121.52639,25.05306,{"lat":589,"lon":588},[592],{"name":106,"role":86,"phone":593,"phoneExt":58,"email":58},"+886223123456x67680",{"facility":595,"status":92,"city":584,"state":58,"zip":596,"country":541,"countryCode":542,"cosmosGeoPoint":597,"geoPoint":599,"contacts":600},"Taipei Veterans General Hospital ( Site 1005)","11217",{"type":99,"coordinates":598},[588,589],{"lat":589,"lon":588},[601],{"name":106,"role":86,"phone":602,"phoneExt":58,"email":58},"+886228712121",{"facility":604,"status":92,"city":605,"state":58,"zip":606,"country":541,"countryCode":542,"cosmosGeoPoint":607,"geoPoint":611,"contacts":612},"Chang Gung Memorial Hospital - Linkou Branch ( Site 1006)","Taoyuan","33305",{"type":99,"coordinates":608},[609,610],121.29696,24.99368,{"lat":610,"lon":609},[613],{"name":106,"role":86,"phone":614,"phoneExt":58,"email":58},"+88633281200 #8825",{"facility":616,"status":92,"city":617,"state":618,"zip":619,"country":620,"countryCode":621,"cosmosGeoPoint":622,"geoPoint":626,"contacts":627},"Ramathibodi Hospital ( Site 1103)","Ratchathewi","Bangkok","10400","Thailand","TH",{"type":99,"coordinates":623},[624,625],100.53358,13.759,{"lat":625,"lon":624},[628],{"name":106,"role":86,"phone":629,"phoneExt":58,"email":58},"+6622004029",{"facility":631,"status":92,"city":632,"state":633,"zip":634,"country":620,"countryCode":621,"cosmosGeoPoint":635,"geoPoint":639,"contacts":640},"Songklanagarind hospital ( Site 1101)","Hat Yai","Changwat Songkhla","90110",{"type":99,"coordinates":636},[637,638],100.47668,7.00836,{"lat":638,"lon":637},[641],{"name":106,"role":86,"phone":642,"phoneExt":58,"email":58},"+6674451469",{"type":644,"investigatorFullName":58,"investigatorTitle":58,"investigatorAffiliation":58,"oldNameTitle":58,"oldOrganization":58},"SPONSOR",[646],{"name":647,"class":6},"Daiichi Sankyo","100576040","phase-1-substudy-06e-umbrella-study-of-combination-therapies-in-esophageal-cancer-mk-3475-06ekeymaker-u06-100576040",false,"NCT06780111","Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E\u002FKEYMAKER-U06)","A Phase 1\u002F2 Open-Label, Umbrella Platform Design Study of Investigational Agents in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy in Participants With 1L Locally Advanced Unresectable\u002FMetastatic Esophageal Cancer: KEYMAKER-U06 Substudy 06E","Inclusion Criteria\n\nThe main inclusion criteria include but are not limited to the following:\n\n* Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic squamous cell carcinoma of the esophagus in first-line (1L) setting.\n* Has measurable disease per RECIST 1.1 as assessed by the local site. investigator or designee\u002Fradiology assessment and verified by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.\n* Has had AEs due to previous anticancer therapies that have recovered to ≤Grade 1 or baseline. Endocrine-related AEs that are adequately treated with hormone replacement are elegible.\n* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART).\n* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n* Has adequate organ function.\n\nExclusion Criteria\n\nThe main exclusion criteria include but are not limited to the following:\n\n* Has had systemic anticancer therapy for locally advanced unresectable or metastatic esophageal cancer.\n* Has tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula.\n* Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention.\n* Has clinically significant corneal disease, history of documented severe dry eye syndrome, severe Meibomian gland disease and\u002For blepharitis, or severe corneal disease that prevents\u002Fdelays corneal healing.\n* HIV-infected participants with a history of Kaposi's sarcoma and\u002For Multicentric Castleman's Disease.\n* Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.\n* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention.\n* Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.\n* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.\n* Has inadequate cardiac function assessed as by a corrected QT interval by Fredericia (QTcF) value ≥470 msec.\n* Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.\n* Has peripheral neuropathy ≥ Grade 2.\n* Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.\n* Has known additional malignancy that is progressing or has required active treatment within the past 3 years.\n* Has known active central nervous system (CNS) metastases and\u002For carcinomatous meningitis.\n* Has active autoimmune disease that has required systemic treatment in the past 2 years.\n* Has had a history of interstitial lung disease (ILD)\u002Fpneumonitis irrespective of steroid use (except for a history of radiation pneumonitis that did not require steroids), has a current diagnosis of ILD, or has clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out.\n* Has active infection requiring systemic therapy.\n* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder.","ALL","18 Years",{"count":658,"type":659},298,"ESTIMATED","INTERVENTIONAL",[662,663],"PHASE1","PHASE2","Researchers are looking for new ways to treat esophageal squamous cell carcinoma (ESCC). ESCC is a type of cancer that starts in certain cells that line the esophagus. The esophagus is the tube that connects the throat to the stomach. This study will look at ESCC that is either locally advanced unresectable, which means it has spread into tissue near where it started and cannot be completely removed by surgery, or metastatic, which means it has spread to other body parts.\n\nAvailable treatments for these types of ESCC include pembrolizumab and chemotherapy. Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Chemotherapy is medicine that destroys cancer cells or stops them from growing.\n\nResearchers want to learn about giving pembrolizumab and investigational agents, with or without chemotherapy to treat ESCC. Ifinatamab deruxtecan (I-DXd), is an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells.\n\nThe main goal of this study is to learn about the safety of investigational agents and pembrolizumab with or without chemotherapy and if people tolerate them. Researchers also want to learn how cancer responds (gets smaller or goes away) to the study treatments.",[666],"Esophageal Squamous Cell Carcinoma","2026-06-25",{"date":669,"type":670},"2026-06-29","ACTUAL",{"date":672,"type":670},"2025-07-30",{"date":674,"type":659},"2032-01-04",{"name":5,"class":6},43]