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NCT05319730PHASE1, PHASE2Recruiting

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)

Merck Sharp & Dohme LLC

Start Date

5/16/2023

Completion Date

4/10/2029

Summary

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

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Paclitaxel

DRUG

Irinotecan

BIOLOGICAL

Pembrolizumab

BIOLOGICAL

MK-4830

DRUG

Lenvatinib

BIOLOGICAL

Sacituzumab tirumotecan

DRUG

Antihistamine

DRUG

H2 Receptor Antagonist

DRUG

Acetaminophen (or equivalent)

DRUG

Dexamethasone (or equivalent)

DRUG

Steroid Mouthwash (dexamethasone or equivalent)

DRUG

Supportive care measures

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Conditions

Esophageal Squamous Cell Carcinoma

Locations

University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 4927)

Tucson, Arizona 85719

United States

UCLA Hematology/Oncology - Santa Monica ( Site 4905)

Los Angeles, California 90404

United States

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

East Syracuse, New York 13057

United States

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

New York, New York 10032

United States

UPMC Hillman Cancer Center-UPMC ( Site 4904)

Pittsburgh, Pennsylvania 15232

United States

Liga Norte Riograndense Contra o Câncer ( Site 4303)

Natal, Rio Grande do Norte 59062-000

Brazil

Hospital Nossa Senhora da Conceição ( Site 4301)

Porto Alegre, Rio Grande do Sul 91350-200

Brazil

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

São Paulo, 01246-000

Brazil

FALP-UIDO ( Site 4400)

Santiago, Region M. de Santiago 7500921

Chile

Centro de Oncología de Precisión-Oncology ( Site 4404)

Santiago, Region M. de Santiago 7560908

Chile

Clínica las Condes ( Site 4403)

Santiago, Region M. de Santiago 7591047

Chile

Clínica UC San Carlos de Apoquindo ( Site 4405)

Santiago, Region M. de Santiago 7620002

Chile

Anhui Provincial Hospital ( Site 3501)

Hefei, Anhui 230001

China

Beijing Cancer hospital-Digestive Oncology ( Site 3500)

Beijing, Beijing Municipality 100142

China

The First Affiliated Hospital of Xiamen University ( Site 3516)

Xiamen, Fujian 361003

China

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

Xinxiang, Henan 453100

China

Henan Cancer Hospital ( Site 3518)

Zhengzhou, Henan 450008

China

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

Huai'an, Jiangsu 223300

China

Shanghai Chest Hospital-Esophageal surgery department ( Site 3513)

Shanghai, Shanghai Municipality 200030

China

Zhejiang Cancer Hospital-Thoracic oncology ( Site 3511)

Hangzhou, Zhejiang 310022

China

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

Frankfurt am Main, Hesse 60488

Germany

Universitaetsklinikum Duesseldorf ( Site 4802)

Düsseldorf, North Rhine-Westphalia 40225

Germany

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

Dresden, Saxony 01307

Germany

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

Berlin, 13353

Germany

Facharztzentrum Eppendorf ( Site 4807)

Hamburg, 20249

Germany

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

Meldola, Emilia-Romagna 47014

Italy

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

Milan, Lombardy 20133

Italy

Azienda Ospedaliero Universitaria Pisana ( Site 3206)

Pisa, Tuscany 56126

Italy

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

Padova, Veneto 35128

Italy

Ospedale San Raffaele-Oncologia Medica ( Site 3202)

Milan, 20132

Italy

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

Milan, 20141

Italy

Aichi Cancer Center ( Site 3702)

Nagoya, Aichi-ken 464-8681

Japan

National Cancer Center Hospital East ( Site 3701)

Kashiwa, Chiba 277-8577

Japan

Saitama Prefectural Cancer Center ( Site 3703)

Kitaadachi-gun, Saitama 3620806

Japan

Shizuoka Cancer Center ( Site 3704)

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

Japan

National Cancer Center Hospital ( Site 3700)

Chuo-ku, Tokyo 104-0045

Japan

Oslo universitetssykehus, Radiumhospitalet ( Site 4501)

Oslo, 0379

Norway

National University Hospital ( Site 3800)

Singapore, South West 119074

Singapore

Asan Medical Center-Department of Oncology ( Site 3901)

Seoul, 05505

South Korea

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

Seoul, 06351

South Korea

Hôpitaux Universitaires de Genève (HUG) ( Site 4702)

Geneva, Canton of Geneva 1211

Switzerland

Kantonsspital Graubünden-Medizin ( Site 4700)

Chur, Kanton Graubünden 7000

Switzerland

Chang Gung Memorial Hospital at Kaohsiung ( Site 4003)

Kaohsiung Niao Sung Dist, Kaohsiung 83301

Taiwan

China Medical University Hospital ( Site 4007)

Taichung, 404332

Taiwan

Taichung Veterans General Hospital-Radiation Oncology ( Site 4008)

Taichung, 407

Taiwan

National Cheng Kung University Hospital ( Site 4001)

Tainan, 704

Taiwan

National Taiwan University Hospital ( Site 4000)

Taipei, 10002

Taiwan

Taipei Veterans General Hospital ( Site 4005)

Taipei, 112

Taiwan

Chang Gung Medical Foundation-Linkou Branch ( Site 4006)

Taoyuan, 33305

Taiwan

Faculty of Medicine Siriraj Hospital ( Site 4102)

Bangkoknoi, Bangkok 10700

Thailand

Chulalongkorn University ( Site 4104)

Pathumwan, Bangkok 10330

Thailand

Songklanagarind hospital ( Site 4105)

Hat Yai, Changwat Songkhla 90110

Thailand

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

Adana, 01140

Turkey (Türkiye)

Hacettepe Universite Hastaneleri-oncology hospital ( Site 3402)

Ankara, 06230

Turkey (Türkiye)

Memorial Ankara Hastanesi-Medical Oncology ( Site 3408)

Ankara, 06520

Turkey (Türkiye)

Ankara Bilkent City Hospital-Medical Oncology ( Site 3405)

Ankara, 06800

Turkey (Türkiye)

Atatürk Üniversitesi-onkoloji ( Site 3416)

Erzurum, 25070

Turkey (Türkiye)

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

Istanbul, 34722

Turkey (Türkiye)

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

Izmir, 35575

Turkey (Türkiye)