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Combination Therapies for Advanced Gastroesophageal Adenocarcinoma

This study is for people with advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma that has already been treated with one type of therapy. It's testing different combinations of medicines: sacituzumab tirumotecan plus paclitaxel, or HER3-DXd plus ramucirumab, or ramucirumab plus paclitaxel. The main goal is to see how safe these combinations are, specifically looking at side effects and how many people experience them. This study is also looking at how well these treatments work. You would be eligible if you are 18 or older and have this specific type of cancer that has spread or cannot be removed by surgery. The study is currently unclear on its recruitment status and plans to enroll about 210 participants.

Study design
This is a Phase 1/2, open-label study, meaning both you and your doctors will know which treatment you are receiving. It's part of a larger study and aims to enroll about 210 participants.
What's involved
Not specified in the trial record.
Compensation
Not stated in the trial record.
Follow-up
The study will track side effects for up to about 60 days during the initial safety phase.

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

NCT06445972

Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06)

Recruiting
PHASE1Ages 18+InterventionalTreatment
Merck Sharp & Dohme LLC
~210 participants
Updated 2026-09-03 on ClinicalTrials.gov
What's tested:RamucirumabPaclitaxelSacituzumab TirumotecanRescue MedicationsHER3-DXd

At a glance

Recruiting sites
44 of 46 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase
Measured over Up to ~28 days
+3 more outcomes measured

Conditions

Gastroesophageal Junction
Gastroesophageal Adenocarcinoma
Esophageal Neoplasms
Esophageal Cancer

Explore related trials

Esophageal AdenocarcinomaGastric AdenocarcinomaGastroesophageal Junction Adenocarcinoma

NCT06445972

Where you'd take part

This study runs at 46 sites. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.

  • Asan Medical Center-Department of Oncology ( Site 7901)

    Seoul, South Koreastudy coordinator listed

    Recruiting

  • Azienda Ospedaliero Universitaria Pisana ( Site 7206)

    Pisa, Tuscany, Italystudy coordinator listed

    Recruiting

  • Beijing Cancer hospital-Digestive Oncology ( Site 7500)

    Beijing, Beijing Municipality, Chinastudy coordinator listed

    Recruiting

  • Bradford Hill Norte ( Site 8407)

    Antofagasta, Chilestudy coordinator listed

    Recruiting

  • Bradfordhill-Clinical Area ( Site 8401)

    Santiago, Region M. de Santiago, Chilestudy coordinator listed

    Recruiting

  • Centre Hospitalier Régional Universitaire de Brest - Hôpital-Institut de cancérologie et hématologi ( Site 7104)

    Brest, Finistere, Francestudy coordinator listed

    Recruiting

  • Centro de Investigación del Maule ( Site 8408)

    Talca, Maule Region, Chilestudy coordinator listed

    Recruiting

  • Centro de Oncología de Precisión-Oncology ( Site 8404)

    Santiago, Region M. de Santiago, Chilestudy coordinator listed

    Recruiting

Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.

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

Opens a ready-to-send draft in your own email app — review before sending.

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Eligibility criteria

Inclusion

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

Exclusion

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
Has known active central nervous system metastases and/or carcinomatous meningitis
Has an active infection requiring systemic therapy
Has concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid) and Hepatitis C virus (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid) infection
History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, or where suspected ILD or pneumonitis cannot be ruled out by imaging at screening
Has severe hypersensitivity (Grade ≥3) to MK-2870, or HER3-DXd, any of their excipients, and/or to another biologic therapy
Has not adequately recovered from major surgery or have ongoing surgical complications

What this trial measures

  • Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In PhaseUp to ~28 days

    DLTs are defined as any drug-related adverse event (AE) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. The percentage of participants who experience at least one DLT will be presented.

  • Percentage of Particiapants who Experience an Adverse Event (AE) During the Safety Lead-In PhaseUp to ~60 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. The percentage of participants who discontinued study intervention due to an AE will be presented.

  • Percentage of Participants who Discontinue Study Intervention Due to an AE During the Safety Lead-In PhaseUp to ~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. The percentage of participants who discontinued study intervention due to an AE will be presented.

  • Objective Response Rate (ORR)Up to ~28 months

    ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.