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A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B)

NCT ID: NCT05319730

Last Updated: 2025-11-10

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

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

230 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-16

Study Completion Date

2029-04-10

Brief Summary

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This is a Phase 1/2, multicenter, randomized, open-label umbrella platform study to evaluate the safety and efficacy of investigational agents with or without pembrolizumab and/or chemotherapy, for the treatment of participants with second line (2L) esophageal squamous cell carcinoma (ESCC) who have previously been exposed to PD-1/PD-L1 based treatment.

Detailed Description

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The master protocol is MK-3475-U06.

As of Protocol Amendment 5, the Pembrolizumab Plus MK-4830 Plus Paclitaxel/Irinotecan arm and the Pembrolizumab Plus MK-4830 Plus Lenvatinib arm are no longer actively enrolling participants.

Conditions

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Esophageal Squamous Cell Carcinoma

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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Paclitaxel or irinotecan

Participants receive paclitaxel 80-100 mg/m\^2 intravenously (IV) on Days 1, 8, and 15 every 28-day cycle until progressive disease (PD) or discontinuation, or irinotecan 180 mg/m\^2 IV on day 1 of every 14-day cycle until PD or discontinuation.

Group Type ACTIVE_COMPARATOR

Paclitaxel

Intervention Type DRUG

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

Irinotecan

Intervention Type DRUG

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

Pembrolizumab + MK-4830 + paclitaxel or irinotecan

Participants receive pembrolizumab 200 mg IV once every 3 weeks (Q3W) for up to 35 cycles (cycle=21 days) or until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + paclitaxel 80-100 mg/m\^2 IV on Days 1, 8, and 15 every 28-day cycle until PD or discontinuation or irinotecan 180 mg/m\^2 180 mg/m\^2 on day 1 every 14-day cycle until PD or discontinuation.

Group Type EXPERIMENTAL

Paclitaxel

Intervention Type DRUG

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

Irinotecan

Intervention Type DRUG

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

Pembrolizumab

Intervention Type BIOLOGICAL

200 mg IV infusion, administered every Q3W up to 35 infusions.

MK-4830

Intervention Type BIOLOGICAL

800 mg IV infusion, administered Q3W up to 35 infusions.

Pembrolizumab + MK-4830 + lenvatinib

Participants receive pembrolizumab 200 mg IV Q3W up to 35 cycles (cycle=21 days) until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + lenvatinib 20 mg oral administration every day until PD or discontinuation.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

200 mg IV infusion, administered every Q3W up to 35 infusions.

MK-4830

Intervention Type BIOLOGICAL

800 mg IV infusion, administered Q3W up to 35 infusions.

Lenvatinib

Intervention Type DRUG

20 mg oral administration every day.

Sacituzumab tirumotecan 4 mg/kg

Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation.

Group Type EXPERIMENTAL

Sacituzumab tirumotecan

Intervention Type BIOLOGICAL

4 mg/kg or 5 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.

Antihistamine

Intervention Type DRUG

Administered per product label.

H2 Receptor Antagonist

Intervention Type DRUG

Administered per product label.

Acetaminophen (or equivalent)

Intervention Type DRUG

Administered per product label.

Dexamethasone (or equivalent)

Intervention Type DRUG

Administered per product label.

Steroid Mouthwash (dexamethasone or equivalent)

Intervention Type DRUG

Administered per product label.

Supportive care measures

Intervention Type DRUG

Participants are allowed to take supportive care measures for the management of adverse events associated with study intervention at the discretion of the investigator. Artificial tear drops or ointment may be given as a supportive care for Ocular Surface Toxicity.

Sacituzumab tirumotecan 5 mg/kg

Participants will receive 5 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation.

Group Type EXPERIMENTAL

Sacituzumab tirumotecan

Intervention Type BIOLOGICAL

4 mg/kg or 5 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.

Antihistamine

Intervention Type DRUG

Administered per product label.

H2 Receptor Antagonist

Intervention Type DRUG

Administered per product label.

Acetaminophen (or equivalent)

Intervention Type DRUG

Administered per product label.

Dexamethasone (or equivalent)

Intervention Type DRUG

Administered per product label.

Steroid Mouthwash (dexamethasone or equivalent)

Intervention Type DRUG

Administered per product label.

Supportive care measures

Intervention Type DRUG

Participants are allowed to take supportive care measures for the management of adverse events associated with study intervention at the discretion of the investigator. Artificial tear drops or ointment may be given as a supportive care for Ocular Surface Toxicity.

Interventions

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Paclitaxel

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

Intervention Type DRUG

Irinotecan

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

Intervention Type DRUG

Pembrolizumab

200 mg IV infusion, administered every Q3W up to 35 infusions.

Intervention Type BIOLOGICAL

MK-4830

800 mg IV infusion, administered Q3W up to 35 infusions.

Intervention Type BIOLOGICAL

Lenvatinib

20 mg oral administration every day.

Intervention Type DRUG

Sacituzumab tirumotecan

4 mg/kg or 5 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.

Intervention Type BIOLOGICAL

Antihistamine

Administered per product label.

Intervention Type DRUG

H2 Receptor Antagonist

Administered per product label.

Intervention Type DRUG

Acetaminophen (or equivalent)

Administered per product label.

Intervention Type DRUG

Dexamethasone (or equivalent)

Administered per product label.

Intervention Type DRUG

Steroid Mouthwash (dexamethasone or equivalent)

Administered per product label.

Intervention Type DRUG

Supportive care measures

Participants are allowed to take supportive care measures for the management of adverse events associated with study intervention at the discretion of the investigator. Artificial tear drops or ointment may be given as a supportive care for Ocular Surface Toxicity.

Intervention Type DRUG

Other Intervention Names

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MK-3475 KEYTRUDA® anti-immunoglobulin-like transcript 4 (anti-ILT4) MK-7902 LENVIMA® SKB264 MK-2870 sac-TMT

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable esophageal squamous cell carcinoma (ESCC)
* Has experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy, that includes a platinum agent and previous exposure to an anti-programmed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1) based immune oncology (IO) therapy
* Has provided an archival or most recent tumor tissue sample obtained as part of clinical practice
* 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 history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* 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
* Participants with human immunodeficiency virus (HIV) with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* History of allogenic tissue/solid organ transplant
* Clinically significant cardiovascular disease within 12 months from first dose of study intervention
* Has risk for significant gastrointestinal (GI) bleeding such as a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization, 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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University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 4927)

Tucson, Arizona, United States

Site Status RECRUITING

UCLA Hematology/Oncology - Santa Monica ( Site 4905)

Los Angeles, California, United States

Site Status RECRUITING

Hematology-Oncology Associates of Central NY, P.C. ( Site 4925)

East Syracuse, New York, United States

Site Status RECRUITING

Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 4907)

New York, New York, United States

Site Status COMPLETED

UPMC Hillman Cancer Center-UPMC ( Site 4904)

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Liga Norte Riograndense Contra o Câncer ( Site 4303)

Natal, Rio Grande do Norte, Brazil

Site Status RECRUITING

Hospital Nossa Senhora da Conceição ( Site 4301)

Porto Alegre, Rio Grande do Sul, Brazil

Site Status RECRUITING

ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 4300)

São Paulo, , Brazil

Site Status RECRUITING

FALP-UIDO ( Site 4400)

Santiago, Region M. de Santiago, Chile

Site Status RECRUITING

Centro de Oncología de Precisión-Oncology ( Site 4404)

Santiago, Region M. de Santiago, Chile

Site Status RECRUITING

Clínica las Condes ( Site 4403)

Santiago, Region M. de Santiago, Chile

Site Status COMPLETED

Clínica UC San Carlos de Apoquindo ( Site 4405)

Santiago, Region M. de Santiago, Chile

Site Status RECRUITING

Anhui Provincial Hospital South District ( Site 3501)

Hefei, Anhui, China

Site Status RECRUITING

Beijing Cancer hospital-Digestive Oncology ( Site 3500)

Beijing, Beijing Municipality, China

Site Status RECRUITING

The First Affiliated Hospital of Xinxiang Medical University-Oncology ( Site 3510)

Xinxiang, Henan, China

Site Status RECRUITING

First Huai'an Hospital Affiliated to Nanjing Medical University ( Site 3506)

Huai'an, Jiangsu, China

Site Status RECRUITING

Shanghai Chest Hospital-Esophageal surgery department ( Site 3513)

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Zhejiang Cancer Hospital-Thoracic oncology ( Site 3511)

Hangzhou, Zhejiang, China

Site Status RECRUITING

Institut für Klinisch Onkologische Forschung-Klink für Onkologie und Hämatologie ( Site 4801)

Frankfurt am Main, Hesse, Germany

Site Status COMPLETED

Universitaetsklinikum Duesseldorf ( Site 4802)

Düsseldorf, North Rhine-Westphalia, Germany

Site Status COMPLETED

Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 4806)

Dresden, Saxony, Germany

Site Status RECRUITING

Charité Campus Virchow-Klinikum-Klinik Hämatologie Onkologie Tumorimmunologie ( Site 4804)

Berlin, , Germany

Site Status COMPLETED

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 3207)

Meldola, Emilia-Romagna, Italy

Site Status RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 3200)

Milan, Lombardy, Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria Pisana ( Site 3206)

Pisa, Tuscany, Italy

Site Status RECRUITING

Istituto Oncologico Veneto IRCCS-Oncologia Medica 1 ( Site 3203)

Padua, Veneto, Italy

Site Status RECRUITING

Ospedale San Raffaele-Oncologia Medica ( Site 3202)

Milan, , Italy

Site Status RECRUITING

Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative ( Site 3201)

Milan, , Italy

Site Status COMPLETED

Aichi Cancer Center ( Site 3702)

Nagoya, Aichi-ken, Japan

Site Status RECRUITING

National Cancer Center Hospital East ( Site 3701)

Kashiwa, Chiba, Japan

Site Status RECRUITING

Saitama Prefectural Cancer Center ( Site 3703)

Kitaadachi-gun, Saitama, Japan

Site Status RECRUITING

Shizuoka Cancer Center ( Site 3704)

Nagaizumi-cho,Sunto-gun, Shizuoka, Japan

Site Status RECRUITING

National Cancer Center Hospital ( Site 3700)

Chuo-ku, Tokyo, Japan

Site Status RECRUITING

Oslo universitetssykehus, Radiumhospitalet ( Site 4501)

Oslo, , Norway

Site Status RECRUITING

National University Hospital ( Site 3800)

Singapore, South West, Singapore

Site Status RECRUITING

Asan Medical Center-Department of Oncology ( Site 3901)

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center-Division of Hematology/Oncology ( Site 3900)

Seoul, , South Korea

Site Status RECRUITING

Hôpitaux Universitaires de Genève (HUG) ( Site 4702)

Geneva, Canton of Geneva, Switzerland

Site Status RECRUITING

Kantonsspital Graubünden-Medizin ( Site 4700)

Chur, Kanton Graubünden, Switzerland

Site Status RECRUITING

Chang Gung Memorial Hospital at Kaohsiung ( Site 4003)

Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan

Site Status RECRUITING

China Medical University Hospital ( Site 4007)

Taichung, , Taiwan

Site Status RECRUITING

Taichung Veterans General Hospital-Radiation Oncology ( Site 4008)

Taichung, , Taiwan

Site Status RECRUITING

National Cheng Kung University Hospital ( Site 4001)

Tainan, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital ( Site 4000)

Taipei, , Taiwan

Site Status RECRUITING

Taipei Veterans General Hospital ( Site 4005)

Taipei, , Taiwan

Site Status RECRUITING

Chang Gung Medical Foundation-Linkou Branch ( Site 4006)

Taoyuan District, , Taiwan

Site Status RECRUITING

Chulalongkorn University ( Site 4104)

Bangkok, Bangkok, Thailand

Site Status RECRUITING

Faculty of Medicine Siriraj Hospital ( Site 4102)

Bangkok, Bangkok, Thailand

Site Status RECRUITING

Songklanagarind hospital ( Site 4105)

Hat Yai, Changwat Songkhla, Thailand

Site Status RECRUITING

Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 3417)

Adana, , Turkey (Türkiye)

Site Status RECRUITING

Hacettepe Universite Hastaneleri-oncology hospital ( Site 3402)

Ankara, , Turkey (Türkiye)

Site Status COMPLETED

Memorial Ankara Hastanesi-Medical Oncology ( Site 3408)

Ankara, , Turkey (Türkiye)

Site Status COMPLETED

Ankara Bilkent City Hospital-Medical Oncology ( Site 3405)

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Atatürk Üniversitesi-onkoloji ( Site 3416)

Erzurum, , Turkey (Türkiye)

Site Status RECRUITING

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 3403)

Istanbul, , Turkey (Türkiye)

Site Status RECRUITING

I.E.U. Medical Point Hastanesi-Oncology ( Site 3406)

Izmir, , Turkey (Türkiye)

Site Status COMPLETED

Countries

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

Central Contacts

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Toll Free Number

Role: CONTACT

Phone: 1-888-577-8839

Email: [email protected]

Facility Contacts

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Study Coordinator

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Related Links

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https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

https://msd.trialsummaries.com/Study/StudyDetails?id=26275&tenant=MT_MSD_9011

Plain Language Summary

Other Identifiers

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jRCT2031220582

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-505189-26-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1291-1987

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-3475-06B

Identifier Type: OTHER

Identifier Source: secondary_id

KEYMAKER-U06B

Identifier Type: OTHER

Identifier Source: secondary_id

2021-005443-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-06B

Identifier Type: -

Identifier Source: org_study_id