NCT06780111

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

A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy in Participants With 1L Locally Advanced Unresectable/Metastatic Esophageal Cancer: KEYMAKER-U06 Substudy 06E

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 298 (estimated)
• Sponsor: Merck Sharp & Dohme LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

The master protocol is MK-3475-U06.

Conditions

• Esophageal Squamous Cell Carcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Pembrolizumab	IV infusion
BIOLOGICAL	I-DXd	IV infusion
DRUG	Leucovorin	IV infusion
DRUG	Levoleucovorin	IV infusion
DRUG	5-Fluorouracil (5-FU)	IV Infusion
DRUG	Oxaliplatin	IV infusion
BIOLOGICAL	Sacituzumab tirumotecan	IV infusion
DRUG	Rescue Medication	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

Timeline

• Start date: 2025-07-30
• Primary completion: 2032-01-04
• Completion: 2032-01-04
• First posted: 2025-01-17
• Last updated: 2026-03-31

Locations

42 sites across 15 countries: United States, Brazil, Chile, China, Czechia, France, Germany, Italy, Japan, Norway, Singapore, South Korea, Switzerland, Taiwan, Thailand

Regulatory

• FDA-regulated drug study