Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/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 efficacy of sacituzumab tirumotecan (MK-2870) plus paclitaxel versus ramucirumab plus paclitaxel, and HER3-DXD plus ramucirumab versus ramucirumab plus paclitaxel for the treatment of participants with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, or esophageal adenocarcinoma who have failed 1 prior line of therapy. This is an estimation study, and no formal hypothesis testing will be performed.

Key facts

Study ID

NCT06445972

Run by

Merck Sharp & Dohme LLC

People needed

210

Starts

2024-08-07

Expected to finish

2030-08-08

Last updated by the study team

2026-07-24

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 treated, second line (2L) (received first line (1L) treatment) gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma
• Has metastatic disease or locally advanced, unresectable disease
• Has experienced documented objective radiographic or clinical disease progression during or after 1L therapy containing any platinum/fluoropyrimidine doublet with or without immunotherapy
• Tumor tissue must be confirmed as negative for HER2 expression (IHC 0/1+ or IHC2+/in situ hybridization negative) as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines
• Can provide a core/excisional biopsy of a tumor lesion not previously irradiated (collected from a biopsy performed after the most recent systemic anticancer therapy regimen)
• AEs due to previous anticancer therapies must be ≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone replacement are acceptable
• Has Eastern Cooperative Oncology Group performance status of 0 or 1
• Has a life expectancy of at least 3 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 experienced weight loss >20% over 3 months before the first dose of study intervention
• Has 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 a serious or nonhealing wound or peptic ulcer or bone fracture within 28 days prior to allocation/randomization
• Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea)
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
• Has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to allocation/randomization
• Has uncontrolled arterial hypertension ≥150/≥90 mm mercury (Hg)
• Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
• Has undergone major surgery within 28 days prior to allocation/randomization, or central venous access device placement within 7 days prior to allocation/randomization or planned major surgery following initiation of study treatment
• Is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents
• Is receiving chronic therapy with nonsteroidal anti-inflammatory agents or other antiplatelet agents
• Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to allocation/randomization
• Has significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to study entry
• Has history of GI perforation and/or fistulae within 6 months prior to allocation/randomization
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)- or HER3-targeted agent, topoisomerase 1 inhibitor-based ADC and/or a topoisomerase 1 inhibitor-based chemotherapy, or any previous systemic therapy targeting vascular endothelial growth factor (VEGF) or the vascular endothelial growth factor receptor (VEGFR) signaling pathways
• Has received prior systemic anticancer therapy 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 received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years. Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded

Where it is running

• Taipei Veterans General Hospital ( Site 8005) — Taipei, Taiwan (enrolling)
• UCLA Hematology/Oncology - Santa Monica ( Site 8905) — Los Angeles, California, United States (enrolling)
• National Taiwan University Hospital-Oncology ( Site 8000) — Taipei, Taiwan (enrolling)
• University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 8927) — Tucson, Arizona, United States (enrolling)
• The Cancer and Hematology Centers ( Site 8912) — Grand Rapids, Michigan, United States (enrolling)
• Hematology-Oncology Associates of Central NY, P.C. ( Site 8925) — East Syracuse, New York, United States (enrolling)
• UPMC Hillman Cancer Center-UPMC ( Site 8904) — Pittsburgh, Pennsylvania, United States (enrolling)
• University of Texas MD Anderson Cancer Center ( Site 8920) — Houston, Texas, United States (enrolling)
• Liga Norte Riograndense Contra o Câncer ( Site 8303) — Natal, Rio Grande do Norte, Brazil (enrolling)
• Hospital Nossa Senhora da Conceição ( Site 8301) — Porto Alegre, Rio Grande do Sul, Brazil (enrolling)
• IBCC - Instituto Brasileiro de Controle do Câncer ( Site 8304) — São Paulo, São Paulo, Brazil (enrolling)
• ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 8300) — São Paulo, Brazil (enrolling)
• Clínica Puerto Montt ( Site 8409) — Port Montt, Los Lagos Region, Chile (enrolling)
• Centro de Investigación del Maule ( Site 8408) — Talca, Maule Region, Chile (enrolling)
• FALP-UIDO ( Site 8400) — Santiago, Region M. de Santiago, Chile (enrolling)
• Centro de Oncología de Precisión-Oncology ( Site 8404) — Santiago, Region M. de Santiago, Chile (enrolling)
• Clínica UC San Carlos de Apoquindo ( Site 8405) — Santiago, Region M. de Santiago, Chile (enrolling)
• Bradfordhill-Clinical Area ( Site 8401) — Santiago, Region M. de Santiago, Chile (enrolling)
• Bradford Hill Norte ( Site 8407) — Antofagasta, Chile (enrolling)
• Beijing Cancer hospital-Digestive Oncology ( Site 7500) — Beijing, Beijing Municipality, China (enrolling)
• The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Site 7501) — Fuzhou, Fujian, China (enrolling)
• The First Affiliated hospital of Xiamen University ( Site 7503) — Xiamen, Fujian, China (enrolling)
• Henan Cancer Hospital ( Site 7504) — Zhengzhou, Henan, China (enrolling)
• The First Affiliated Hospital of Nanchang University ( Site 7514) — Nanchang, Jiangxi, China (enrolling)
• Fudan University Shanghai Cancer Center ( Site 7513) — Shanghai, Shanghai Municipality, China (enrolling)

Full record on ClinicalTrials.gov

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