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

NCT ID: NCT05342636

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-27

Study Completion Date

2025-12-05

Brief Summary

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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.

Detailed Description

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The master protocol is MK-3475-U06.

Conditions

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Esophageal Squamous Cell Carcinoma (ESCC)

Keywords

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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)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pembrolizumab plus chemotherapy

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.

Group Type EXPERIMENTAL

Irinotecan

Intervention Type DRUG

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

Paclitaxel

Intervention Type DRUG

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

Pembrolizumab

Intervention Type BIOLOGICAL

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

Coformulation Favezelimab/Pembrolizumab plus Chemotherapy

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.

Group Type EXPERIMENTAL

Irinotecan

Intervention Type DRUG

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

Paclitaxel

Intervention Type DRUG

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

Coformulation favezelimab/pembrolizumab

Intervention Type BIOLOGICAL

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

Pembrolizumab plus MK-4830 plus Chemotherapy

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.

Group Type EXPERIMENTAL

MK-4830

Intervention Type BIOLOGICAL

800 mg administered via IV infusion Q3W

Irinotecan

Intervention Type DRUG

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

Paclitaxel

Intervention Type DRUG

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

Pembrolizumab

Intervention Type BIOLOGICAL

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

Pembrolizumab plus MK-4830 plus lenvatinib

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.

Group Type EXPERIMENTAL

MK-4830

Intervention Type BIOLOGICAL

800 mg administered via IV infusion Q3W

Lenvatinib

Intervention Type DRUG

20 mg administered via oral capsules each day

Pembrolizumab

Intervention Type BIOLOGICAL

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

Interventions

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MK-4830

800 mg administered via IV infusion Q3W

Intervention Type BIOLOGICAL

Lenvatinib

20 mg administered via oral capsules each day

Intervention Type DRUG

Irinotecan

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

Intervention Type DRUG

Paclitaxel

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

Intervention Type DRUG

Pembrolizumab

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

Intervention Type BIOLOGICAL

Coformulation favezelimab/pembrolizumab

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

Intervention Type BIOLOGICAL

Other Intervention Names

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MK-3475 KEYTRUDA® MK-4280A anti-immunoglobulin-like transcript 4 (ILT4) MK-7902 LENVIMA®

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Clinically significant cardiovascular disease within 12 months from first dose of study intervention
* Participants with known gastrointestinal (GI) malabsorption or any other condition that may affect the absorption of lenvatinib
* Has risk for significant GI bleeding, such as:
* Has had a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization
* Has significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Liga Norte Riograndense Contra o Câncer ( Site 2303)

Natal, Rio Grande do Norte, Brazil

Site Status

Hospital Nossa Senhora da Conceição ( Site 2301)

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

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

São Paulo, São Paulo, Brazil

Site Status

FALP-UIDO ( Site 2400)

Santiago, Region M. de Santiago, Chile

Site Status

Clínica las Condes ( Site 2403)

Santiago, Region M. de Santiago, Chile

Site Status

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

Brest, Finistere, France

Site Status

Hopital Claude Huriez - CHU de Lille ( Site 1100)

Lille, Nord, France

Site Status

Pitie Salpetriere University Hospital ( Site 1102)

Paris, Orne, France

Site Status

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

Frankfurt am Main, Hesse, Germany

Site Status

Universitaetsklinikum Duesseldorf ( Site 2802)

Düsseldorf, North Rhine-Westphalia, Germany

Site Status

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

Dresden, Saxony, Germany

Site Status

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

Berlin, , Germany

Site Status

Ospedale San Raffaele-Oncologia Medica ( Site 1206)

Milan, Lombardy, Italy

Site Status

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

Milan, Lombardy, Italy

Site Status

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

Milan, , Italy

Site Status

Istituto Oncologico Veneto IRCCS ( Site 1205)

Padua, , Italy

Site Status

Aichi Cancer Center Hospital ( Site 1702)

Nagoya, Aichi-ken, Japan

Site Status

National Cancer Center Hospital East ( Site 1701)

Kashiwa, Chiba, Japan

Site Status

Saitama Prefectural Cancer Center ( Site 1703)

Ina-machi, Saitama, Japan

Site Status

Shizuoka Cancer Center ( Site 1704)

Nagaizumi-cho,Sunto-gun, Shizuoka, Japan

Site Status

National Cancer Center Hospital ( Site 1700)

Chuo-ku, Tokyo, Japan

Site Status

Oslo universitetssykehus, Radiumhospitalet ( Site 2501)

Oslo, , Norway

Site Status

National University Hospital ( Site 1800)

Singapore, South West, Singapore

Site Status

Asan Medical Center-Department of Oncology ( Site 1901)

Seoul, , South Korea

Site Status

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

Seoul, , South Korea

Site Status

Hôpitaux Universitaires de Genève (HUG) ( Site 2702)

Geneva, Canton of Geneva, Switzerland

Site Status

Kantonsspital Graubünden-Medizin ( Site 2700)

Chur, Kanton Graubünden, Switzerland

Site Status

Chang Gung Memorial Hospital at Kaohsiung ( Site 2003)

Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan

Site Status

China Medical University Hospital ( Site 2007)

Taichung, , Taiwan

Site Status

Taichung Veterans General Hospital-Radiation Oncology ( Site 2008)

Taichung, , Taiwan

Site Status

National Cheng Kung University Hospital ( Site 2001)

Tainan, , Taiwan

Site Status

National Taiwan University Hospital ( Site 2000)

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital ( Site 2005)

Taipei, , Taiwan

Site Status

Chang Gung Medical Foundation-Linkou Branch ( Site 2006)

Taoyuan District, , Taiwan

Site Status

Chulalongkorn University ( Site 2104)

Bangkok, Bangkok, Thailand

Site Status

Faculty of Medicine Siriraj Hospital ( Site 2102)

Bangkok, Bangkok, Thailand

Site Status

Songklanagarind hospital ( Site 2105)

Hat Yai, Changwat Songkhla, Thailand

Site Status

Acibadem Altunizade Hospital-Oncology ( Site 1407)

Üsküdar / İstanbul, Istanbul, Turkey (Türkiye)

Site Status

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

Izmir, Karsiyaka, İzmir, Turkey (Türkiye)

Site Status

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

Adana, , Turkey (Türkiye)

Site Status

Hacettepe Universite Hastaneleri-oncology hospital ( Site 1402)

Ankara, , Turkey (Türkiye)

Site Status

Memorial Ankara Hastanesi-Medical Oncology ( Site 1408)

Ankara, , Turkey (Türkiye)

Site Status

Ankara City Hospital-Medical Oncology ( Site 1405)

Ankara, , Turkey (Türkiye)

Site Status

Akdeniz Universitesi Hastanesi-Medical Oncology ( Site 1410)

Antalya, , Turkey (Türkiye)

Site Status

Atatürk Üniversitesi-onkoloji ( Site 1416)

Erzurum, , Turkey (Türkiye)

Site Status

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

Istanbul, , Turkey (Türkiye)

Site Status

Countries

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Brazil Chile France Germany Italy Japan Norway Singapore South Korea Switzerland Taiwan Thailand Turkey (Türkiye)

Related Links

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Other Identifiers

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2031220197

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-505188-36-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1291-1899

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-005405-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-06A

Identifier Type: -

Identifier Source: org_study_id