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Study of Pembrolizumab and Chemotherapy for Gastroesophageal Adenocarcinoma

This study is looking at new ways to treat advanced gastroesophageal adenocarcinoma (a type of stomach or esophageal cancer) that has not been treated before and cannot be removed by surgery. It combines pembrolizumab (an immunotherapy that helps your immune system fight cancer) with chemotherapy drugs like capecitabine, leucovorin, or levoleucovorin, and an investigational drug called sacituzumab tirumotecan. Researchers want to see how safe these combinations are and what side effects they might cause. This study is for adults aged 18 and older who have this specific type of cancer, and whose tumors are HER2-negative (meaning they don't have high levels of a protein called HER2). The study will first check for safety and then look at how well the treatments work. About 160 people are expected to join.

Study design
This is an open-label (meaning you and your doctors will know what treatment you are receiving) umbrella platform study with two phases: a safety lead-in phase and an efficacy phase. It plans to enroll about 160 participants.
What's involved
The initial safety phase will monitor for dose-limiting toxicities and adverse events for up to approximately 28 days. The study does not specify further details about visits or procedures.
Compensation
Not stated in the trial record.
Follow-up
Safety is measured for up to approximately 28 days. The record does not specify long-term follow-up after this period.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

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)

Recruiting
PHASE1Ages 18+InterventionalTreatment
Merck Sharp & Dohme LLC
~160 participants
Updated 2026-08-25 on ClinicalTrials.gov
What's tested:PembrolizumabSacituzumab Tirumotecan (sac-TMT)CapecitabineLeucovorinLevoleucovorin5-Fluorouracil (5-FU)

At a glance

Recruiting sites
48 of 51 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)
Measured over Up to approximately 28 days
+3 more outcomes measured

Conditions

Gastroesophageal Junction
Gastroesophageal Adenocarcinoma
Esophageal Neoplasms
Esophageal Cancer

Explore related trials

Esophageal AdenocarcinomaEsophageal CarcinomaGastric CarcinomaGastroesophageal Junction Adenocarcinoma

Where it's being run

51 sites across 39 states
Region M. de Santiago4
Taiwan4
Bangkok3
New York2
Brazil2
Fujian2
South Korea2
Arizona1

Study leadership

  • Medical Director · STUDY_DIRECTOR · Merck Sharp & Dohme LLC

Who to contact

Toll Free Number
[email protected]
1-888-577-8839
Email the study team

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Do you actually qualify for this trial?

Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.

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Eligibility criteria

Inclusion

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

Exclusion

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
Has concurrent active hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] positive and/or detectable HBV DNA) and hepatitis C virus (defined as anti-hepatitis C virus \[HCV\] Ab positive and detectable HCV ribonucleic acid \[RNA\] infection or a known history of hepatitis B and/or C infection
Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study
Has gastrointestinal (GI) obstruction, poor oral intake, or difficulty in taking oral medication
Has poorly controlled diarrhea
Has had a major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention
Has history of allogeneic tissue/solid organ transplant
Has not adequately recovered from major surgery or has ongoing surgical complications

What this trial measures

  • Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)Up to approximately 28 days

    DLTs are defined as any treatment-emergent adverse events (TEAEs) not attributable to disease or disease-related processes that occur during the DLT evaluation period and are a Grade 3 or higher according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0. The percentage of participants who experience at least one DLT will be reported.

  • Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE)Up to approximately 28 days

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  • Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AEUp to approximately 28 days

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  • Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)Up to approximately 28 months

    ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.