Open Actively Recruiting

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

About

Brief Summary

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, 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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1/Phase 2

Eligibility

Gender

All

Healthy Volunteers

Minimum Age

18 Years

Maximum Age

N/A

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

Has histologically and/or cytologically confirmed diagnosis of previously treated, 2L (received first line (1L) treatment) gastric adenocarcinoma, GEJ 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
Participants with gastroesophageal adenocarcinoma that is known to be human epidermal growth factor receptor 2 (HER2)/neu positive are excluded. Participants with unknown HER2 status are eligible.
Has provided an archival tumor tissue sample or most recently obtained core, incisional, or excisional biopsy of a tumor lesion
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 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 Criteria:

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 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 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 randomization, or central venous access device placement within 7 days prior to 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 (NSAIDs) or other antiplatelet agents
Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to 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 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)-targeted antibody-drug conjugate (ADC), topoisomerase 1 inhibitor-based ADC and/or a topoisomerase 1 inhibitor-based chemotherapy
Has received 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 including investigational agents within 4 weeks before the first dose of study drug 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 a 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 (CNS) metastases and/or carcinomatous meningitis
Has an active infection requiring systemic therapy
Has a concurrent active HBV (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid) and HCV (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
Has severe hypersensitivity (Grade ≥3) to sacituzumab tirumotecan, any of its excipients and/or to another biologic therapy
Has not adequately recovered from major surgery or have ongoing surgical complications