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

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.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Biological: Pembrolizumab; Drug: Oxaliplatin; Drug: Leucovorin; Biological: Sacituzumab tirumotecan; Drug: Levoleucovorin; Drug: 5-Fluorouracil (5-FU); Biological: I-DXd; Drug: Rescue Medication

Detailed Description

The master protocol is MK-3475-U06.

• Study Type: Interventional
• Enrollment (Estimated): 298
• 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

• Brazil
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil, 59062-000
      • Recruiting
      • Liga Norte Riograndense Contra o Cancer ( Site 1301)
      • Contact: Study Coordinator; Phone Number: +55 84 4009-5595
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 91010-004
      • Recruiting
      • Hospital Nossa Senhora da Conceicao ( Site 1300)
      • Contact: Study Coordinator; Phone Number: +555133572092
• Chile
  • Antofagasta, Chile, 1263521
    • Recruiting
    • Bradford Hill Norte ( Site 1405)
    • Contact: Study Coordinator; Phone Number: +56442023631
  • Los Lagos Region
    • Port Montt, Los Lagos Region, Chile, 5500243
      • Recruiting
      • Clínica Puerto Montt ( Site 1406)
      • Contact: Study Coordinator; Phone Number: +56652484800
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7500921
      • Recruiting
      • FALP ( Site 1400)
      • Contact: Study Coordinator; Phone Number: +56224205098
    • Santiago, Region M. de Santiago, Chile, 7560908
      • Recruiting
      • Centro de Oncología de Precisión ( Site 1402)
      • Contact: Study Coordinator; Phone Number: 56225189885
    • Santiago, Region M. de Santiago, Chile, 7620002
      • Recruiting
      • Clínica UC San Carlos de Apoquindo ( Site 1403)
      • Contact: Study Coordinator; Phone Number: +56223748924
    • Santiago, Region M. de Santiago, Chile, 8420383
      • Recruiting
      • Bradfordhill ( Site 1401)
      • Contact: Study Coordinator; Phone Number: +56220490970
• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • Recruiting
      • The Second Affiliated Hospital of Anhui Medical University ( Site 9511)
      • Contact: Study Coordinator; Phone Number: 0551-63839536
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 130021
      • Recruiting
      • Beijing Cancer Hospital ( Site 9500)
      • Contact: Study Coordinator; Phone Number: (010)88196317
  • Fujian
    • Xiamen, Fujian, China, 361003
      • Recruiting
      • The First Affiliated Hospital of Xiamen University ( Site 9503)
      • Contact: Study Coordinator; Phone Number: 0592-2139767
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Recruiting
      • Henan Cancer Hospital ( Site 9509)
      • Contact: Study Coordinator; Phone Number: 0371-65587625
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • Xuzhou Central Hospital ( Site 9512)
      • Contact: Study Coordinator; Phone Number: 86051680812397
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital of Nanchang University ( Site 9505)
      • Contact: Study Coordinator; Phone Number: 86079188692201
• Czechia
  • Brno-mesto
    • Brno, Brno-mesto, Czechia, 656 53
      • Recruiting
      • Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 9000)
      • Contact: Study Coordinator; Phone Number: +420543136812
• France
  • Paris, France, 75013
    • Recruiting
    • Pitie Salpetriere University Hospital ( Site 9102)
    • Contact: Study Coordinator; Phone Number: +331 42 16 10 41
  • Finistere
    • Brest, Finistere, France, 29609
      • Recruiting
      • C.H.R.U. de Brest - Hopital Cavale Blanche ( Site 9104)
      • Contact: Study Coordinator; Phone Number: 33298223428
  • Nord
    • Lille, Nord, France, 59037
      • Recruiting
      • CHU Lille - Institut Coeur Poumon ( Site 9100)
      • Contact: Study Coordinator; Phone Number: +33320445461
• Germany
  • Hamburg, Germany, 20249
    • Recruiting
    • Haematologisch-Onkologische Praxis Eppendorf Facharztzentrum Eppendorf - Hope ( Site 1807)
    • Contact: Study Coordinator; Phone Number: +4940360352246
  • North Rhine-Westphalia
    • Düsseldorf, North Rhine-Westphalia, Germany, 40225
      • Recruiting
      • Universitaetsklinikum Duesseldorf ( Site 1808)
      • Contact: Study Coordinator; Phone Number: +492118108751
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Recruiting
      • Universitätsklinikum Carl Gustav Carus - Medical Oncology ( Site 1806)
      • Contact: Study Coordinator; Phone Number: +493514583016
• Italy
  • Lombardy
    • Milan, Lombardy, Italy, 20132
      • Recruiting
      • Ospedale San Raffaele-Oncologia Medica ( Site 9201)
      • Contact: Study Coordinator; Phone Number: +390226437615
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Recruiting
      • Istituto Oncologico Veneto IRCCS ( Site 9202)
      • Contact: Study Coordinator; Phone Number: 390498215910
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Recruiting
      • Aichi Cancer Center ( Site 9702)
      • Contact: Study Coordinator; Phone Number: +81-52-762-6111
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East ( Site 9701)
      • Contact: Study Coordinator; Phone Number: +81-4-7133-1111
  • Tokyo
    • Chūō, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital ( Site 9700)
      • Contact: Study Coordinator; Phone Number: +81-3-3542-2511
• Norway
  • Oslo, Norway, 0379
    • Recruiting
    • Oslo Universitetssykehus Radiumhospitalet ( Site 1501)
    • Contact: Study Coordinator; Phone Number: +4723026600
• Singapore
  • Central Singapore
    • Singapore, Central Singapore, Singapore, 119074
      • Recruiting
      • National University Hospital ( Site 9800)
      • Contact: Study Coordinator; Phone Number: +65 6908 2222
• South Korea
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center ( Site 9901)
    • Contact: Study Coordinator; Phone Number: +82230107179
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center ( Site 9900)
    • Contact: Study Coordinator; Phone Number: +82234106518
  • Kyonggi-do
    • Goyang-si, Kyonggi-do, South Korea, 10408
      • Recruiting
      • National Cancer Center ( Site 9902)
      • Contact: Study Coordinator; Phone Number: +82319201694
• Switzerland
  • Geneva, Switzerland, 1211
    • Recruiting
    • Hopitaux Universitaires de Geneve HUG. ( Site 1701)
    • Contact: Study Coordinator; Phone Number: +41 (0)22 372 95 77
  • Kanton Graubünden
    • Chur, Kanton Graubünden, Switzerland, 7000
      • Recruiting
      • Kantonsspital Graubuenden ( Site 1700)
      • Contact: Study Coordinator; Phone Number: +41 81 256 61 11
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Recruiting
    • Kaohsiung Chang Gung Memorial Hospital ( Site 1003)
    • Contact: Study Coordinator; Phone Number: +88677317123x3679
  • Taichung, Taiwan, 40707
    • Recruiting
    • China Medical University Hospital ( Site 1007)
    • Contact: Study Coordinator; Phone Number: 886-4-22052121
  • Tainan, Taiwan, 704
    • Recruiting
    • National Cheng Kung University Hospital ( Site 1001)
    • Contact: Study Coordinator; Phone Number: +88662353535x4559
  • Taipei, Taiwan, 100225
    • Recruiting
    • National Taiwan University Hospital ( Site 1000)
    • Contact: Study Coordinator; Phone Number: +886223123456x67680
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital ( Site 1005)
    • Contact: Study Coordinator; Phone Number: +886228712121
  • Taoyuan, Taiwan, 33305
    • Recruiting
    • Chang Gung Memorial Hospital - Linkou Branch ( Site 1006)
    • Contact: Study Coordinator; Phone Number: +88633281200 #8825
  • Kaohsiung
    • Kaoshiung, Kaohsiung, Taiwan, 807
      • Recruiting
      • Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 1009)
      • Contact: Study Coordinator; Phone Number: +8867-3121101#7451
• Thailand
  • Bangkok
    • Ratchathewi, Bangkok, Thailand, 10400
      • Recruiting
      • Ramathibodi Hospital ( Site 1103)
      • Contact: Study Coordinator; Phone Number: +6622004029
  • Changwat Songkhla
    • Hat Yai, Changwat Songkhla, Thailand, 90110
      • Recruiting
      • Songklanagarind hospital ( Site 1101)
      • Contact: Study Coordinator; Phone Number: +6674451469
• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • UPMC Hillman Cancer Center ( Site 1904)
      • Contact: Study Coordinator; Phone Number: 412-623-8974

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

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

• Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic squamous cell carcinoma of the esophagus in first-line (1L) setting.
• Has measurable disease per RECIST 1.1 as assessed by the local site. investigator or designee/radiology assessment and verified by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
• Has AEs due to previous anticancer therapies of ≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone replacement are acceptable.
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART).
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Has adequate organ function.

Exclusion Criteria

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

• Has had systemic anticancer therapy for locally advanced unresectable or metastatic esophageal cancer.
• Has tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula.
• Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention.
• Has clinically significant corneal disease, history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
• Has received prior systemic anticancer therapy including investigational agents 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 inadequate cardiac function assessed as: - corrected QT interval by Fredericia (QTcF) value >470 msec.
• Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
• Has peripheral neuropathy ≥ Grade 2.
• Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has active autoimmune disease that has required systemic treatment in the past 2 years.
• Has had (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, and/or suspected interstitial lung disease (ILD)/pneumonitis that cannot be ruled out by imaging at Screening.
• Has active infection requiring systemic therapy.
• Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; 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 for Arms 2, 3, and 4, and H1 receptor antagonist, H2 receptor antagonist, acetaminophen, and dexamethasone for Arm 5, administered per approved product label
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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Leucovorin; IV infusion; Drug: Levoleucovorin; IV infusion; Drug: 5-Fluorouracil (5-FU); IV Infusion; 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 for Arms 2, 3, and 4, and H1 receptor antagonist, H2 receptor antagonist, acetaminophen, and dexamethasone for Arm 5, administered per approved product label
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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Oxaliplatin; IV infusion; Drug: Leucovorin; IV infusion; Drug: Levoleucovorin; IV infusion; Drug: 5-Fluorouracil (5-FU); IV Infusion; 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 for Arms 2, 3, and 4, and H1 receptor antagonist, H2 receptor antagonist, acetaminophen, and dexamethasone for Arm 5, administered per approved product label
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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Oxaliplatin; IV infusion; Drug: Leucovorin; IV infusion; Drug: Levoleucovorin; IV infusion; Drug: 5-Fluorouracil (5-FU); IV Infusion
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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Leucovorin; IV infusion; Biological: Sacituzumab tirumotecan; IV infusion; Other Names: SKB264; MK-2870; Drug: Levoleucovorin; IV infusion; Drug: 5-Fluorouracil (5-FU); 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants who Experience an Adverse Event (AE)	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 experience an AE will be reported.	Up to approximately 77 months
Objective Response Rate (ORR)	ORR is defined as a confirmed complete response (CR: the 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 (RECIST) 1.1 as assessed by blinded independent central review (BICR). The percentage of participants who experience CR or PR as assessed by BICR will be presented.	Up to approximately 77 months
Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase	Percentage of participants experiencing toxicities that are possibly, probably, or definitely related to study intervention; that meet pre-defined severity criteria; and result in a change in the given dose.	Up to approximately 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	For participants who demonstrate a confirmed 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 RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until 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 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.	Up to approximately 77 months
Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death from any cause, whichever occurs first. 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 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.	Up to approximately 77 months
Overall Survival (OS)	OS is defined as the time from allocation/randomization to death due to any cause.	Up to approximately 77 months
Disease Control Rate (DCR)	DCR is defined as a confirmed complete response (CR) or partial response (PR), or stable disease (SD) with at least 6 months PFS per RECIST 1.1 as assessed by BICR.	Up to approximately 77 months
Maximum Plasma Concentration (Cmax) of I-DXd	Cmax is defined as the peak level I-DXd reaches in the blood plasma. Blood samples collected predose and at multiple timepoints postdose will be used to determine the Cmax of I-DXd when co-administered with other investigational agents.	At designated time points up to approximately 65 months
Time to Maximum Plasma Concentration (Tmax) of I-DXd	Tmax is defined as the time it took I-DXd to reach its peak level in blood plasma. Blood samples collected predose and at designated timepoints postdose will be used to determine the Tmax of I-DXd when co-administered with other investigational agents.	At designated time points up to approximately 65 months
The Percentage of Participants with Antidrug Antibodies (ADA) Against I-DXd	Blood samples collected at designated timepoints will be used to determine the ADA response to I-DXd. The percentage of participants with ADA will be reported.	Up to approximately 65 months
The Percentage of Participants with Treatment-Emergent ADA Against I-DXd	Blood samples collected at designated timepoints will be used to determine the treatment-emergent ADA response to I-DXd. The percentage of participants who have treatment-emergent I-DXd ADA will be reported.	Up to approximately 65 months
Area Under the Concentration-Time Curve from Time 0 to Last Measurable Plasma Concentration (AUClast) of I-DXd	AUClast is defined as the area under the concentration-time curve from time 0 to the last measurable concentration of I-DXd in the blood plasma. Blood samples collected at predose and at designated timepoints postdose will be used to determine the AUClast of I-DXd in combination with other agents.	At designated time points up to approximately 65 months
Area Under the Concentration-Time Curve from Time 0 to the End of the Dosing Period (AUCtau) of I-DXd	AUCtau is defined as the area under the concentration-time curve from time zero to the end of the dosing period. Blood samples collected at predose and at designated timepoints postdose will be used to determine the AUCtau of I-DXd in combination with other agents.	At designated time points up to approximately 65 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
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2025
• Primary Completion (Estimated): January 4, 2032
• Study Completion (Estimated): January 4, 2032

Study Registration Dates

• First Submitted: January 13, 2025
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): January 17, 2025

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 10, 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; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzymes and Coenzymes; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Fluorouracil; Leucovorin; Levoleucovorin; pembrolizumab
• Other Study ID Numbers: 3475-06E; MK-3475-06E (Other Identifier: MSD); U1111-1307-6484 (Registry Identifier: UTN); jRCT2041240166 (Registry Identifier: Japan Registry of Clinical Trials (jRCT)); 2024-514273-22-00 (Registry Identifier: EU CT)

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