A Study of Combination Therapies With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer (MK-3475-06A)

NCT05342636 | Completed Phase 1 FDA Drug

• 5 other identifiers: 3475-06A20312201972023-505188-36-00U1111-1291-18992021-005405-26
• Study Type: interventional
• Target: 90
• Locations: 13 countries
• Sites: 46

Brief Summary

This is a phase I/II multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of investigational agents with pembrolizumab, plus chemotherapy or lenvatinib, for the treatment of participants with advanced esophageal cancer who have failed 1 prior line of therapy and have not been previously exposed to programmed cell death 1 protein (PD-1)/ programmed cell death ligand 1 (PD-L1) based treatment. With protocol amendment 5 (effective: 17-November-2023), enrollment in study arms "Pembrolizumab plus MK-4830 plus Chemotherapy" and "Pembrolizumab plus MK-4830 plus lenvatinib" is discontinued.

Conditions

Esophageal Squamous Cell Carcinoma (ESCC)

Keywords

Esophageal cancer; Programmed Cell Death 1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL-1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL-2, PD-L2)

Outcome Measures

Primary Outcomes (4)

• Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase

  A DLT is defined as any drug-related adverse event (AE) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle.

  Up to approximately 3 weeks

• Number of Participants Experiencing an Adverse Event (AE) During Safety Lead-in Phase

  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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  Up to approximately 3 Weeks

• Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase

  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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  Up to approximately 3 weeks

• 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 40 months

Secondary Outcomes (5)

• Progression-Free Survival (PFS)

  Up to approximately 40 months

• Duration of Response (DOR)

  Up to approximately 40 months

• Overall Survival (OS)

  Up to approximately 40 months

• Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase

  Up to approximately 40 months

• Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase

  Up to approximately 104 weeks

Study Arms (4)

Pembrolizumab plus chemotherapy

EXPERIMENTAL

Participants will receive pembrolizumab intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Biological: Pembrolizumab; Drug: Irinotecan; Drug: Paclitaxel

Coformulation Favezelimab/Pembrolizumab plus Chemotherapy

EXPERIMENTAL

Participants will receive coformulation of favezelimab/pembrolizumab administered intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Biological: Coformulation favezelimab/pembrolizumab; Drug: Irinotecan; Drug: Paclitaxel

Pembrolizumab plus MK-4830 plus Chemotherapy

EXPERIMENTAL

Participants will receive pembrolizumab intravenously plus MK-4830 plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Biological: Pembrolizumab; Biological: MK-4830; Drug: Irinotecan; Drug: Paclitaxel

Pembrolizumab plus MK-4830 plus lenvatinib

EXPERIMENTAL

Participants will receive pembrolizumab intravenously plus MK-4830 plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Biological: Pembrolizumab; Biological: MK-4830; Drug: Lenvatinib

Interventions

Lenvatinib DRUG

20 mg administered via oral capsules each day

Also known as: MK-7902, LENVIMA®

Pembrolizumab plus MK-4830 plus lenvatinib

Irinotecan DRUG

180 mg/m\^2 administered via IV infusion on day 1 of every 14-day cycle.

Coformulation Favezelimab/Pembrolizumab plus Chemotherapy; Pembrolizumab plus MK-4830 plus Chemotherapy; Pembrolizumab plus chemotherapy

Paclitaxel DRUG

80-100 mg/m\^2 administered via IV infusion on Days 1, 8 and 15 of every 28 day cycle

Coformulation Favezelimab/Pembrolizumab plus Chemotherapy; Pembrolizumab plus MK-4830 plus Chemotherapy; Pembrolizumab plus chemotherapy

Pembrolizumab BIOLOGICAL

200 mg administered via intravenous (IV) infusion every 3 weeks (Q3W)

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab plus MK-4830 plus Chemotherapy; Pembrolizumab plus MK-4830 plus lenvatinib; Pembrolizumab plus chemotherapy

Coformulation favezelimab/pembrolizumab BIOLOGICAL

800 mg favezelimab + 200 mg pembrolizumab administered via IV infusion on day 1 and then Q3W

Also known as: MK-4280A

Coformulation Favezelimab/Pembrolizumab plus Chemotherapy

MK-4830 BIOLOGICAL

800 mg administered via IV infusion Q3W

Also known as: anti-immunoglobulin-like transcript 4 (ILT4)

Pembrolizumab plus MK-4830 plus Chemotherapy; Pembrolizumab plus MK-4830 plus lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable ESCC
• Has experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy.
• Has an evaluable baseline tumor sample (newly obtained or archival) for analysis
• Has adequately controlled blood pressure (BP) with or without antihypertensive medications
• Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible
• Direct invasion into adjacent organs such as the aorta or trachea
• Has experienced weight loss \>10% over approximately 2 months prior to first dose of study therapy
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
• Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has undergone potentially curative therapy
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Active autoimmune disease that has required systemic treatment in past 2 years
• History of human immunodeficiency virus (HIV) infection
• History of Hepatitis B or known active Hepatitis C virus infection
• History of allogenic tissue/solid organ transplant

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (46)

Liga Norte Riograndense Contra o Câncer ( Site 2303)

Natal, Rio Grande do Norte, 59062-000, Brazil

Location

Hospital Nossa Senhora da Conceição ( Site 2301)

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 2300)

São Paulo, São Paulo, 01246-000, Brazil

Location

FALP-UIDO ( Site 2400)

Santiago, Region M. de Santiago, 7500921, Chile

Location

Clínica las Condes ( Site 2403)

Santiago, Region M. de Santiago, 7591047, Chile

Location

Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan ( Site 1104)

Brest, Finistere, 29200, France

Location

Hopital Claude Huriez - CHU de Lille ( Site 1100)

Lille, Nord, 59037, France

Location

Pitie Salpetriere University Hospital ( Site 1102)

Paris, Orne, 75013, France

Location

Institut für Klinisch Onkologische Forschung-Klink für Onkologie und Hämatologie ( Site 2801)

Frankfurt am Main, Hesse, 60488, Germany

Location

Universitaetsklinikum Duesseldorf ( Site 2802)

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 2806)

Dresden, Saxony, 01307, Germany

Location

Charité Campus Virchow-Klinikum-Klinik Hämatologie Onkologie Tumorimmunologie ( Site 2804)

Berlin, 13353, Germany

Location

Ospedale San Raffaele-Oncologia Medica ( Site 1206)

Milan, Lombardy, 20132, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1200)

Milan, Lombardy, 20133, Italy

Location

Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative (

Milan, 20141, Italy

Location

Istituto Oncologico Veneto IRCCS ( Site 1205)

Padua, 35128, Italy

Location

Aichi Cancer Center Hospital ( Site 1702)

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East ( Site 1701)

Kashiwa, Chiba, 277-8577, Japan

Location

Saitama Prefectural Cancer Center ( Site 1703)

Ina-machi, Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center ( Site 1704)

Nagaizumi-cho,Sunto-gun, Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital ( Site 1700)

Chuo-ku, Tokyo, 104-0045, Japan

Location

Oslo universitetssykehus, Radiumhospitalet ( Site 2501)

Oslo, 0310, Norway

Location

National University Hospital ( Site 1800)

Singapore, South West, 119074, Singapore

Location

Asan Medical Center-Department of Oncology ( Site 1901)

Seoul, 05505, South Korea

Location

Samsung Medical Center-Division of Hematology/Oncology ( Site 1900)

Seoul, 06351, South Korea

Location

Hôpitaux Universitaires de Genève (HUG) ( Site 2702)

Geneva, Canton of Geneva, 1211, Switzerland

Location

Kantonsspital Graubünden-Medizin ( Site 2700)

Chur, Kanton Graubünden, 7000, Switzerland

Location

Chang Gung Memorial Hospital at Kaohsiung ( Site 2003)

Kaohsiung Niao Sung Dist, Kaohsiung, 83301, Taiwan

Location

China Medical University Hospital ( Site 2007)

Taichung, 404332, Taiwan

Location

Taichung Veterans General Hospital-Radiation Oncology ( Site 2008)

Taichung, 407, Taiwan

Location

National Cheng Kung University Hospital ( Site 2001)

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 2000)

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital ( Site 2005)

Taipei, 112, Taiwan

Location

Chang Gung Medical Foundation-Linkou Branch ( Site 2006)

Taoyuan District, 333, Taiwan

Location

Chulalongkorn University ( Site 2104)

Bangkok, Bangkok, 10330, Thailand

Location

Faculty of Medicine Siriraj Hospital ( Site 2102)

Bangkok, Bangkok, 10700, Thailand

Location

Songklanagarind hospital ( Site 2105)

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

Acibadem Altunizade Hospital-Oncology ( Site 1407)

Üsküdar / İstanbul, Istanbul, 34662, Turkey (Türkiye)

Location

I.E.U. Medical Point Hastanesi-Oncology ( Site 1406)

Izmir, Karsiyaka, İzmir, 009035575, Turkey (Türkiye)

Location

Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 1417)

Adana, 01140, Turkey (Türkiye)

Location

Hacettepe Universite Hastaneleri-oncology hospital ( Site 1402)

Ankara, 06230, Turkey (Türkiye)

Location

Memorial Ankara Hastanesi-Medical Oncology ( Site 1408)

Ankara, 06520, Turkey (Türkiye)

Location

Ankara City Hospital-Medical Oncology ( Site 1405)

Ankara, 06800, Turkey (Türkiye)

Location

Akdeniz Universitesi Hastanesi-Medical Oncology ( Site 1410)

Antalya, 07059, Turkey (Türkiye)

Location

Atatürk Üniversitesi-onkoloji ( Site 1416)

Erzurum, 25070, Turkey (Türkiye)

Location

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1403)

Istanbul, 34722, Turkey (Türkiye)

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; lenvatinib; Irinotecan; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2022
• First Posted: April 22, 2022
• Study Start: July 27, 2022
• Primary Completion: December 5, 2025
• Study Completion: December 5, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

IT (4); BR (3); DE (4); CL (2); CH (2); SG (1); KR (2); TW (7); JP (5); NO (1); TH (3); TU (9); FR (3)