A Clinical Trial of Ifinatamab Deruxtecan in People With Advanced Esophageal Cancer (MK-3475-06F)

A Phase 2 Open-Label, Umbrella Platform Design Study of Investigational Agent(s) in Participants With 2L/3L Unresectable Locally Advanced or Metastatic Esophageal Cancer: KEYMAKER-U06 Substudy 06F

The purpose of this trial is to assess if ifinatamab deruxtecan (I-DXd) can treat esophageal squamous cell carcinoma (ESCC). 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 goal of this trial is to learn how many participants who receive I-DXd have the cancer respond, which means the cancer gets smaller or goes away.

Study Overview

• Status: Recruiting
• Conditions: Oesophageal Squamous Cell Carcinoma
• Intervention / Treatment: Biological: I-DXd; Drug: Rescue Medication

Detailed Description

The master screening protocol is MK-3475-U06 (KEYMAKER-U06)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@msd.com

Study Locations

• Czechia
  • Brno-mesto
    • Brno, Brno-mesto, Czechia, 565 53
      • Recruiting
      • Masarykuv onkologicky ustav ( Site 4000)
      • Contact: Study Coordinator; Phone Number: +420543131111
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Recruiting
      • Aichi Cancer Center ( Site 2702)
      • Contact: Study Coordinator; Phone Number: +81-52-762-6111
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Recruiting
      • Kanagawa Cancer Center ( Site 2701)
      • Contact: Study Coordinator; Phone Number: +81-45-520-2222
  • Tokyo
    • Chūō, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital ( Site 2700)
      • Contact: Study Coordinator; Phone Number: +81-3-3542-2511
• Norway
  • Oslo, Norway, 0379
    • Recruiting
    • Oslo universitetssykehus, Radiumhospitalet ( Site 3501)
    • Contact: Study Coordinator; Phone Number: +4722934000
• South Korea
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center ( Site 2900)
    • Contact: Study Coordinator; Phone Number: +82234101796
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center ( Site 2901)
    • Contact: Study Coordinator; Phone Number: +82230101120
  • Kyonggi-do
    • Goyang-si, Kyonggi-do, South Korea, 10408
      • Recruiting
      • National Cancer Center ( Site 2902)
      • Contact: Study Coordinator; Phone Number: +8219200440
• Switzerland
  • Geneva, Switzerland, 1211
    • Recruiting
    • Hopitaux Universitaires de Geneve HUG ( Site 3701)
    • Contact: Study Coordinator; Phone Number: +41 22 372 29 01
  • Kanton Graubünden
    • Chur, Kanton Graubünden, Switzerland, 7000
      • Recruiting
      • Kantonsspital Graubünden-Medizin ( Site 3700)
      • Contact: Study Coordinator; Phone Number: +41 81 256 61 11
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Recruiting
    • Chang Gung Memorial Hospital at Kaohsiung ( Site 3003)
    • Contact: Study Coordinator; Phone Number: +88677317123
  • Taichung, Taiwan, 40447
    • Recruiting
    • China Medical University Hospital ( Site 3007)
    • Contact: Study Coordinator; Phone Number: 886-4-22052121
  • Tainan, Taiwan, 704
    • Recruiting
    • National Cheng Kung University Hospital ( Site 3001)
    • Contact: Study Coordinator; Phone Number: +886-6-235-3535
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital ( Site 3000)
    • Contact: Study Coordinator; Phone Number: +886-2-23123456
  • Taipei, Taiwan, 106
    • Recruiting
    • National Taiwan University Cancer Center (NTUCC) ( Site 3010)
    • Contact: Study Coordinator; Phone Number: +886223220322
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital ( Site 3005)
    • Contact: Study Coordinator; Phone Number: 886-2-28717270
  • Taoyuan, Taiwan, 33305
    • Recruiting
    • Chang Gung Memorial Hospital - Linkou Branch ( Site 3006)
    • Contact: Study Coordinator; Phone Number: +88633281200

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)
• Has disease progression after 1 or 2 prior lines of systemic therapy for unresectable locally advanced or metastatic ESCC
• Has measurable disease
• If infected with human immunodeficiency virus (HIV), has well-controlled HIV on antiretroviral therapy
• Has adequate organ function

Exclusion Criteria:

• Has histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma subtype
• Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention
• Has clinically significant corneal disease
• Has any of the following within 6 months before screening: cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event
• If infected with HIV, has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has uncontrolled or significant cardiovascular disease
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known active central nervous system metastases and/or carcinomatous meningitis
• Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, except for a history of radiation pneumonitis that did not require steroids or has current diagnosis of ILD or has clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out
• Has active infection requiring systemic therapy other than those permitted.
• Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc), and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc), prior pneumonectomy, or requirement for supplemental oxygen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I-DXd; Participants will be administered I-DXd every 3 weeks until progressive disease or discontinuation criteria are met.	Biological: I-DXd; IV Infusion; Other Names: DS-7300a; MK-2400; Ifinatamab Deruxtecan; Drug: Rescue Medication; Includes 5-HT3 receptor antagonist, NK-1 receptor antagonist, and corticosteroid, administered per approved product label

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	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.	Up to approximately 14 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	For participants who demonstrate a confirmed CR (disappearance of all target lesions) or (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.	Up to approximately 18 months
Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by RECIST 1.1. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.	Up to approximately 18 months
Number of Participants Who Experience an Adverse Events (AEs)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.	Up to approximately 18 months
Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.	Up to approximately 18 months
Overall Survival (OS)	OS is defined as time from randomization to death due to any cause.	Up to approximately 26 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Daiichi Sankyo
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2026
• Primary Completion (Estimated): June 12, 2027
• Study Completion (Estimated): June 12, 2028

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: February 5, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma
• Other Study ID Numbers: 3475-06F; U1111-1329-6558 (Other Identifier: UTN); MK-3475-06F (Other Identifier: MSD); 2026-525213-31-00 (Registry Identifier: EU CT); jRCT2041250179 (Registry Identifier: jRCT(Japan Registry of Clinical Trials))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No