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OncoMatch/Clinical Trials/NCT06469944

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)

Is NCT06469944 recruiting? Yes, currently enrolling (Sep 2026). This Phase 1/2 trial studies multiple treatments for gastroesophageal junction.

Phase 1/2RecruitingMerck Sharp & Dohme LLCNCT06469944Data as of Sep 2026Location: International · 12 countries

Treatment: Pembrolizumab · Sacituzumab Tirumotecan (sac-TMT) · Capecitabine · Leucovorin · Levoleucovorin · 5-Fluorouracil (5-FU) · Oxaliplatin · Patritumab DeruxtecanThis 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.

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Extracted eligibility criteria

Treatments studied

Immunotherapy

Pembrolizumab

Targeted therapy

Patritumab Deruxtecan

Chemotherapy

Capecitabine5-Fluorouracil (5-FU)Oxaliplatin

Other

Sacituzumab Tirumotecan (sac-TMT)LeucovorinLevoleucovorin

Cancer type

Gastric Cancer

Esophageal Carcinoma

Biomarker criteria

Required: HER2 (ERBB2) wild-type (absence)

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

Performance status

ECOG 0–1(Restricted strenuous activity)

Prior therapy

Max 0 prior lines

Cannot have received: systemic anticancer therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ)/esophageal adenocarcinoma

Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ)/esophageal adenocarcinoma

Cannot have received: TROP2-targeted agent

Has received prior treatment with a trophoblast antigen 2 (TROP2)-targeted ... agent

Cannot have received: anti-HER3 targeted agent

Has received prior treatment with ... anti-human epidermal growth factor receptor 3 (HER3) targeted agents

Cannot have received: topoisomerase I inhibitor-based antibody-drug conjugate

Has received prior treatment with a topoisomerase I inhibitor-based antibody-drug conjugate (ADC)

Cannot have received: topoisomerase I inhibitor-based chemotherapy

Has received prior treatment with ... topoisomerase I inhibitor-based chemotherapy

Cannot have received: anti-PD-1/PD-L1/PD-L2 or co-inhibitory T-cell receptor therapy

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)

Lab requirements

Blood counts

Has adequate organ function

Kidney function

Has adequate organ function

Liver function

Has adequate organ function

Has adequate organ function

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 6927) · Tucson, Arizona
  • UCLA Hematology/Oncology - Santa Monica ( Site 6905) · Los Angeles, California
  • Norton Hospital-Norton Cancer Institute - Downtown ( Site 6900) · Louisville, Kentucky
  • The Cancer and Hematology Centers ( Site 6912) · Grand Rapids, Michigan
  • Hematology-Oncology Associates of Central NY, P.C. ( Site 6925) · East Syracuse, New York

Showing up to 5 US sites.

See all sites on ClinicalTrials.gov →

Frequently asked questions

Is NCT06469944 currently recruiting?

Yes, this trial is currently recruiting patients.

Are there prior therapy exclusions?

Yes. Prior systemic anticancer therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ)/esophageal adenocarcinoma, TROP2-targeted agent, anti-HER3 targeted agent disqualifies patients from enrollment.

Does this trial require ERBB2?

Yes, ERBB2 wild-type is a required biomarker for enrollment.

Could you qualify for this trial?

Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.

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