Substudy 06C: A Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06)
Recruiting now · Phase 1/Phase 2
Conditions studied: Gastroesophageal Junction, Gastroesophageal Adenocarcinoma, Esophageal Neoplasms, Esophageal Cancer
In brief
This is a phase 1/2, multicenter, open-label umbrella platform study that will evaluate the safety and tolerability of investigational agents with pembrolizumab and fluoropyrimidine chemotherapy for the first-line (1L) treatment of participants with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma. This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for investigational agents in combination with chemotherapy and immunotherapy. There is no formal hypothesis in this study.
Key facts
- Study ID
- NCT06469944
- Run by
- Merck Sharp & Dohme LLC
- People needed
- 160
- Starts
- 2024-09-20
- Expected to finish
- 2029-09-12
- Last updated by the study team
- 2026-08-07
Who can join
Age: 18 and older. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- The main inclusion criteria include but are not limited to the following:
- Has histologically and/or cytologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic first-line (1L) gastroesophageal adenocarcinoma
- Is not expected to require tumor resection during the treatment course
- Tumor tissue must be confirmed as negative for human epidermal growth factor receptor 2 (HER2) expression as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines
- Core/excisional biopsy of a tumor lesion not previously irradiated has been provided
- Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline
- Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible
- Has adequate organ function
- Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the local site investigator/radiology assessment and verified by blinded independent central review (BICR)
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to the first dose of study intervention
- Has a life expectancy of at least 6 months
- 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 prior to allocation/randomization
- Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable at screening
- Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
You may not qualify if…
- The main exclusion criteria include but are not limited to the following:
- Has squamous cell or undifferentiated gastroesophageal cancer.
- Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ)/esophageal adenocarcinoma
- Has experienced weight loss >20% over 3 months before the first dose of study intervention
- Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
- Has Grade ≥2 peripheral neuropathy
- Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within 6 months preceding study intervention
- Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
- Has history of human immunodeficiency virus (HIV) infection with Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Has received prior treatment with a trophoblast antigen 2 (TROP2)-targeted or anti-human epidermal growth factor receptor 3 (HER3) targeted agents
- Has received prior treatment with a topoisomerase I inhibitor-based antibody-drug conjugate (ADC) and/or a topoisomerase I inhibitor-based chemotherapy
- Has received prior systemic anticancer therapy within 4 weeks before the first dose of study intervention
- Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR)
- 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
- Has received a strong inducer/inhibitor of CYP3A4 that cannot be discontinued
- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
- Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy 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 Severe hypersensitivity (≥Grade 3) to pembrolizumab, sacituzumab tirumotecan, patritumab deruxtecan, or other biologic therapy, chemotherapy (ie, oxaliplatin, fluorouracil, capecitabine), leucovorin, levoleucovorin, or any of their excipients
- Has active autoimmune disease that has required systemic treatment in the past 2 years
- Has history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at Screening
- Has an active infection requiring systemic therapy
Where it is running
- UCLA Hematology/Oncology - Santa Monica ( Site 6905) — Los Angeles, California, United States (enrolling)
- Sir Run Run Shaw Hospital of Zhejiang University School of Medicine ( Site 5510) — Hangzhou, Zhejiang, China (enrolling)
- The Cancer and Hematology Centers ( Site 6912) — Grand Rapids, Michigan, United States (enrolling)
- Hematology-Oncology Associates of Central NY, P.C. ( Site 6925) — East Syracuse, New York, United States (enrolling)
- University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 6927) — Tucson, Arizona, United States (enrolling)
- UPMC Hillman Cancer Center-UPMC ( Site 6904) — Pittsburgh, Pennsylvania, United States (enrolling)
- University of Texas MD Anderson Cancer Center ( Site 6920) — Houston, Texas, United States (enrolling)
- Liga Norte Riograndense Contra o Câncer ( Site 6303) — Natal, Rio Grande do Norte, Brazil (enrolling)
- Hospital Nossa Senhora da Conceição ( Site 6301) — Porto Alegre, Rio Grande do Sul, Brazil (enrolling)
- ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 6300) — São Paulo, Brazil (enrolling)
- IBCC - Instituto Brasileiro de Controle do Câncer ( Site 6304) — São Paulo, Brazil (enrolling)
- Clínica Puerto Montt ( Site 6409) — Port Montt, Los Lagos Region, Chile (enrolling)
- Centro de Investigación del Maule ( Site 6408) — Talca, Maule Region, Chile (enrolling)
- FALP-UIDO ( Site 6400) — Santiago, Region M. de Santiago, Chile (enrolling)
- Centro de Oncología de Precisión-Oncology ( Site 6404) — Santiago, Region M. de Santiago, Chile (enrolling)
- Clínica UC San Carlos de Apoquindo ( Site 6405) — Santiago, Region M. de Santiago, Chile (enrolling)
- Bradfordhill-Clinical Area ( Site 6401) — Santiago, Region M. de Santiago, Chile (enrolling)
- Bradford Hill Norte ( Site 6407) — Antofagasta, Chile (enrolling)
- Beijing Cancer hospital-Digestive Oncology ( Site 5500) — Beijing, Beijing Municipality, China (enrolling)
- The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Site 5501) — Fuzhou, Fujian, China (enrolling)
- The First Affiliated hospital of Xiamen University ( Site 5503) — Xiamen, Fujian, China (enrolling)
- Henan Cancer Hospital ( Site 5504) — Zhengzhou, Henan, China (enrolling)
- The First Affiliated Hospital of Nanchang University ( Site 5514) — Nanchang, Jiangxi, China (enrolling)
- Fudan University Shanghai Cancer Center ( Site 5513) — Shanghai, Shanghai Municipality, China (enrolling)
- CHU-BREST Cavale Blanche ( Site 5104) — Brest, Finistere, France (enrolling)
Full record on ClinicalTrials.gov
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