Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E/KEYMAKER-U06)
NCT ID: NCT06780111
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
228 participants
INTERVENTIONAL
2025-07-30
2032-01-04
Brief Summary
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Available 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.
Researchers want to learn about giving pembrolizumab and ifinatamab deruxtecan (I-DXd), a study medicine, with or without chemotherapy to treat ESCC. I-DXd is an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells.
The main goal of this study is to learn about the safety of I-DXd 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.
Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Pembrolizumab + Chemotherapy
Participants will receive 200 mg of pembrolizumab via intravenous (IV) infusion every three weeks (Q3W) on Day 1 of each 21 day cycle up to 35 cycles (up to approximately 2 years), and mFOLFOX6 chemotherapy: oxaliplatin 85 mg/m\^2 via IV infusion every 2 weeks (Q2W) until progressive disease (PD) or toxicity; leucovorin 400 mg/m2 OR levoleucovorin 200 mg/m\^2 via IV infusion Q2W until PD or toxicity; 5-fluorouracil (5-FU) 400 mg/m\^2 bolus IV infusion followed by 2400 mg/m\^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity.
Pembrolizumab
IV infusion
Leucovorin
IV infusion
Levoleucovorin
IV infusion
5-Fluorouracil (5-FU)
IV Infusion
Oxaliplatin
IV infusion
Pembrolizumab + I-DXd
Participants will receive 200 mg of pembrolizumab via IV infusion Q3W on Day 1 of each 21 day cycle for up to 35 cycles (up to approximately 2 years). Participants will also receive up to 12 mg/kg I-XDd Q3W via IV infusion until PD or toxicity.
Pembrolizumab
IV infusion
I-DXd
IV infusion
Pembrolizumab + I-DXd + 5-FU IV + Leucovorin or Levoleucovorin
Participants will receive 200 mg 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 I-DXd up to 12 mg/kg via IV infusion Q3W until PD or toxicity, 5-FU 400 mg/m\^2 bolus IV infusion followed by 2400 mg/m\^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity, and leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 via IV infusion Q2W until PD or toxicity.
Pembrolizumab
IV infusion
I-DXd
IV infusion
Leucovorin
IV infusion
Levoleucovorin
IV infusion
5-Fluorouracil (5-FU)
IV Infusion
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/kg I-DXd via IV infusion q3w until PD or toxicity, 5-FU 2400 mg/m\^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity, 60mg/m\^2 oxaliplatin via IV infusion Q2W until PD or toxicity, and leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 via IV infusion Q2W until PD or toxicity.
Pembrolizumab
IV infusion
I-DXd
IV infusion
Leucovorin
IV infusion
Levoleucovorin
IV infusion
5-Fluorouracil (5-FU)
IV Infusion
Oxaliplatin
IV infusion
Interventions
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Pembrolizumab
IV infusion
I-DXd
IV infusion
Leucovorin
IV infusion
Levoleucovorin
IV infusion
5-Fluorouracil (5-FU)
IV Infusion
Oxaliplatin
IV infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Has measurable disease per RECIST 1.1 as assessed by the local site. investigator/radiology assessment and verified by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
* Has AEs due to previous anticancer therapies of ≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone replacement are acceptable.
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART).
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load.
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Exclusion Criteria
* Has tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula.
* Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention.
* Has clinically significant corneal disease.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* 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
* Has received prior treatment with orlotamab, enoblituzumab, or other humanized anti-B7 homologue 3 (B7-H3)-targeted agents.
* Has received prior treatment with a topoisomerase-I inhibitor, including antibody-drug conjugate (ADC).
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention.
* Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
* Has inadequate cardiac function assessed as: - corrected QT interval by Fredericia (QTcF) value \>470 msec.
* 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.
* Has peripheral neuropathy ≥ Grade 2.
* 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.
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has active autoimmune disease that has required systemic treatment in the past 2 years.
* Has had (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, and/or suspected interstitial lung disease (ILD)/pneumonitis that cannot be ruled out by imaging at Screening.
* Has active infection requiring systemic therapy.
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder.
* Has severe hypersensitivity (≥Grade 3) to treatment with a monoclonal antibody (mAb) or known sensitivity or intolerance to pembrolizumab, I-DXd, study chemotherapy agents and/or to any of their excipients, murine proteins, or platinum containing products.
* Has had allogeneic tissue/solid organ transplant.
* Have not adequately recovered from major surgery or have ongoing surgical complications.
* Are incapacitated.
18 Years
ALL
No
Sponsors
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Daiichi Sankyo
INDUSTRY
Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
Locations
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Liga Norte Riograndense Contra o Cancer ( Site 1301)
Natal, Rio Grande do Norte, Brazil
Clínica Puerto Montt ( Site 1406)
Port Montt, Los Lagos Region, Chile
FALP ( Site 1400)
Santiago, Region M. de Santiago, Chile
Centro de Oncología de Precisión ( Site 1402)
Santiago, Region M. de Santiago, Chile
Clínica UC San Carlos de Apoquindo ( Site 1403)
Santiago, Region M. de Santiago, Chile
The Second Affiliated Hospital of Anhui Medical University ( Site 9511)
Hefei, Anhui, China
Beijing Cancer Hospital ( Site 9500)
Beijing, Beijing Municipality, China
The First Affiliated Hospital of Xiamen University ( Site 9503)
Xiamen, Fujian, China
Henan Cancer Hospital ( Site 9509)
Zhengzhou, Henan, China
Xuzhou Central Hospital ( Site 9512)
Xuzhou, Jiangsu, China
The First Affiliated Hospital of Nanchang University ( Site 9505)
Nanchang, Jiangxi, China
Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 9000)
Brno, Brno-mesto, Czechia
CHU Lille - Institut Coeur Poumon ( Site 9100)
Lille, Nord, France
Pitie Salpetriere University Hospital ( Site 9102)
Paris, , France
Ospedale San Raffaele-Oncologia Medica ( Site 9201)
Milan, Lombardy, Italy
Istituto Oncologico Veneto IRCCS ( Site 9202)
Padua, Veneto, Italy
Aichi Cancer Center ( Site 9702)
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital East ( Site 9701)
Kashiwa, Chiba, Japan
National Cancer Center Hospital ( Site 9700)
Chūō, Tokyo, Japan
Oslo Universitetssykehus Radiumhospitalet ( Site 1501)
Oslo, , Norway
National University Hospital ( Site 9800)
Singapore, Central Singapore, Singapore
National Cancer Center ( Site 9902)
Goyang-si, Kyonggi-do, South Korea
Asan Medical Center ( Site 9901)
Seoul, , South Korea
Kantonsspital Graubuenden ( Site 1700)
Chur, Kanton Graubünden, Switzerland
Hopitaux Universitaires de Geneve HUG. ( Site 1701)
Geneva, , Switzerland
Kaohsiung Chang Gung Memorial Hospital ( Site 1003)
Kaohsiung City, , Taiwan
National Cheng Kung University Hospital ( Site 1001)
Tainan, , Taiwan
National Taiwan University Hospital ( Site 1000)
Taipei, , Taiwan
Taipei Veterans General Hospital ( Site 1005)
Taipei, , Taiwan
Ramathibodi Hospital ( Site 1103)
Ratchathewi, Bangkok, Thailand
Countries
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Central Contacts
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Facility Contacts
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Related Links
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Merck Clinical Trials Information
Other Identifiers
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MK-3475-06E
Identifier Type: OTHER
Identifier Source: secondary_id
2024-514273-22-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
U1111-1307-6484
Identifier Type: REGISTRY
Identifier Source: secondary_id
jRCT2041240166
Identifier Type: REGISTRY
Identifier Source: secondary_id
3475-06E
Identifier Type: -
Identifier Source: org_study_id