Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E/KEYMAKER-U06)

Part of paid clinical trials in Pittsburgh, Pennsylvania.

Sponsor
Merck Sharp & Dohme LLC
Study ID
NCT06780111
Phase
PHASE1/PHASE2
Status
Recruiting
Apply to this trial

Conditions

  • Esophageal Squamous Cell Carcinoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Pembrolizumab — BIOLOGICAL
    IV infusion
  • I-DXd — BIOLOGICAL
    IV infusion
  • Leucovorin — DRUG
    IV infusion
  • Levoleucovorin — DRUG
    IV infusion
  • 5-Fluorouracil (5-FU) — DRUG
    IV Infusion
  • Oxaliplatin — DRUG
    IV infusion
  • Sacituzumab tirumotecan — BIOLOGICAL
    IV infusion
  • Rescue Medication — DRUG
    Includes 5-HT3 receptor antagonist, NK-1 receptor antagonist, and corticosteroid for Arms 2, 3, and 4, and H1 receptor antagonist, H2 receptor antagonist, acetaminophen, and dexamethasone for Arm 5, administered per approved product label

Study Details

Researchers are looking for new ways to treat esophageal squamous cell carcinoma (ESCC). ESCC is a type of cancer that starts in certain cells that line the esophagus. The esophagus is the tube that connects the throat to the stomach. This study will look at ESCC that is either locally advanced unresectable, which means it has spread into tissue near where it started and cannot be completely removed by surgery, or metastatic, which means it has spread to other body parts. Available treatments for these types of ESCC include pembrolizumab and chemotherapy. Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Chemotherapy is medicine that destroys cancer cells or stops them from growing. Researchers want to learn about giving pembrolizumab and investigational agents, with or without chemotherapy to treat ESCC. Ifinatamab deruxtecan (I-DXd), is an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. The main goal of this study is to learn about the safety of investigational agents and pembrolizumab with or without chemotherapy and if people tolerate them. Researchers also want to learn how cancer responds (gets smaller or goes away) to the study treatments.

Key Dates

Start date
Jul 30, 2025
Status verified
Mar 2026
Primary completion
Jan 4, 2032
Completion
Jan 4, 2032

Study Design

Enrollment
298 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Pembrolizumab + Chemotherapy
    Participants will receive 400 mg of pembrolizumab via intravenous (IV) infusion every six weeks (Q6W) on Day 1 of each 42 day cycle up to 18 cycles (up to approximately 2 years), and mFOLFOX6 chemotherapy: oxaliplatin 85 mg/m\^2 via IV infusion every 2 weeks (Q2W) until progressive disease (PD) or toxicity; leucovorin 400 mg/m2 OR levoleucovorin 200 mg/m\^2 via IV infusion Q2W until PD or toxicity; 5-fluorouracil (5-FU) 400 mg/m\^2 bolus IV infusion followed by 2400 mg/m\^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity.
  • Experimental: Pembrolizumab + I-DXd
    Participants will receive 200 mg of pembrolizumab via IV infusion Q3W on Day 1 of each 21 day cycle for up to 35 cycles (up to approximately 2 years). Participants will also receive up to 12 mg/kg I-XDd Q3W via IV infusion until PD or toxicity.
  • Experimental: Pembrolizumab + I-DXd + 5-FU IV + Leucovorin or Levoleucovorin
    Participants will receive 200 mg pembrolizumab via IV infusion Q3W on Day 1 of each 21 day cycle up to 35 cycles (up to approximately 2 years). Participants will also receive I-DXd up to 12 mg/kg via IV infusion Q3W until PD or toxicity, 5-FU 400 mg/m\^2 bolus IV infusion followed by 2400 mg/m\^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity, and leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 via IV infusion Q2W until PD or toxicity.
  • Experimental: Pembrolizumab + I-DXd + 5-FU IV + Leucovorin or Levoleucovorin + Oxaliplatin
    Participants will receive 200 mg of pembrolizumab via IV infusion Q3W on Day 1 of each 21 day cycle up to 35 cycles (up to approximately 2 years). Participants will also receive up to 12 mg/kg I-DXd via IV infusion q3w until PD or toxicity, 5-FU 2400 mg/m\^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity, 60mg/m\^2 oxaliplatin via IV infusion Q2W until PD or toxicity, and leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 via IV infusion Q2W until PD or toxicity.
  • Experimental: Pembrolizumab + Sacituzumab tirumotecan + 5-FU IV + Leucovorin or Levoleucovorin
    Participants will receive 400 mg pembrolizumab via IV infusion Q6W on Day 1 of each 42 day cycle up to 18 cycles (up to approximately 2 years). Participants will also receive sacituzumab tirumotecan 4 mg/kg via IV infusion Days 1, 15, and 29 every 42 day cycle until PD or toxicity, 5-FU 400 mg/m\^2 bolus IV infusion followed by 2400 mg/m\^2 continuous 46-48 hour IV infusion Q2W until PD or toxicity, and leucovorin 400 mg/m\^2 OR levoleucovorin 200 mg/m\^2 via IV infusion Q2W until PD or toxicity.

Primary Outcome Measure

Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase [ Time Frame: Up to approximately 28 days ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
UPMC Hillman Cancer Center ( Site 1904)PittsburghPennsylvania15232
Study Coordinator
412-623-8974

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By research site
UPMC Hillman Cancer Center· Pittsburgh, PA

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