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)

NCT05319730 | Recruiting Phase 1 FDA Drug

• 7 other identifiers: 3475-06BjRCT20312205822023-505189-26-00U1111-1291-1987MK-3475-06BKEYMAKER-U06B2021-005443-76
• Study Type: interventional
• Target: 230
• Locations: 14 countries
• Sites: 59

Brief 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.

Conditions

Esophageal Squamous Cell Carcinoma

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 Dose-Limiting Toxicities (DLTs) During Safety Lead-in Phase

  A DLT is defined as any drug-related 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 Who Experienced 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.

  Up to approximately 3 weeks

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

  An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.

  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 48 months

Secondary Outcomes (5)

• Progression-Free Survival (PFS)

  Up to approximately 70 months

• Duration of Response (DOR)

  Up to approximately 70 months

• Overall Survival (OS)

  Up to approximately 70 months

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

  Up to approximately 70 months

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

  Up to approximately 70 months

Study Arms (5)

Paclitaxel or irinotecan

ACTIVE COMPARATOR

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.

Drug: Paclitaxel; Drug: Irinotecan

Pembrolizumab + MK-4830 + paclitaxel or irinotecan

EXPERIMENTAL

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.

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

Pembrolizumab + MK-4830 + lenvatinib

EXPERIMENTAL

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.

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

Sacituzumab tirumotecan 4 mg/kg

EXPERIMENTAL

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.

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

Sacituzumab tirumotecan 5 mg/kg

EXPERIMENTAL

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.

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

Interventions

Paclitaxel DRUG

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

Paclitaxel or irinotecan; Pembrolizumab + MK-4830 + paclitaxel or irinotecan

Irinotecan DRUG

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

Paclitaxel or irinotecan; Pembrolizumab + MK-4830 + paclitaxel or irinotecan

Pembrolizumab BIOLOGICAL

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

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab + MK-4830 + lenvatinib; Pembrolizumab + MK-4830 + paclitaxel or irinotecan

MK-4830 BIOLOGICAL

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

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

Pembrolizumab + MK-4830 + lenvatinib; Pembrolizumab + MK-4830 + paclitaxel or irinotecan

Sacituzumab tirumotecan BIOLOGICAL

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

Also known as: SKB264, MK-2870, sac-TMT

Sacituzumab tirumotecan 4 mg/kg; Sacituzumab tirumotecan 5 mg/kg

Lenvatinib DRUG

20 mg oral administration every day.

Also known as: MK-7902, LENVIMA®

Pembrolizumab + MK-4830 + lenvatinib

H2 Receptor Antagonist DRUG

Administered per product label.

Sacituzumab tirumotecan 4 mg/kg; Sacituzumab tirumotecan 5 mg/kg

Acetaminophen (or equivalent) DRUG

Administered per product label.

Sacituzumab tirumotecan 4 mg/kg; Sacituzumab tirumotecan 5 mg/kg

Antihistamine DRUG

Administered per product label.

Sacituzumab tirumotecan 4 mg/kg; Sacituzumab tirumotecan 5 mg/kg

Dexamethasone (or equivalent) DRUG

Administered per product label.

Sacituzumab tirumotecan 4 mg/kg; Sacituzumab tirumotecan 5 mg/kg

Steroid Mouthwash (dexamethasone or equivalent) DRUG

Administered per product label.

Sacituzumab tirumotecan 4 mg/kg; Sacituzumab tirumotecan 5 mg/kg

Supportive care measures 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 4 mg/kg; Sacituzumab tirumotecan 5 mg/kg

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 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
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (59)

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

Tucson, Arizona, 85719, United States

RECRUITING

UCLA Hematology/Oncology - Santa Monica ( Site 4905)

Los Angeles, California, 90404, United States

RECRUITING

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

East Syracuse, New York, 13057, United States

RECRUITING

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

New York, New York, 10032, United States

COMPLETED

UPMC Hillman Cancer Center-UPMC ( Site 4904)

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Liga Norte Riograndense Contra o Câncer ( Site 4303)

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

RECRUITING

Hospital Nossa Senhora da Conceição ( Site 4301)

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

RECRUITING

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

São Paulo, 01246-000, Brazil

RECRUITING

FALP-UIDO ( Site 4400)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Centro de Oncología de Precisión-Oncology ( Site 4404)

Santiago, Region M. de Santiago, 7560908, Chile

RECRUITING

Clínica las Condes ( Site 4403)

Santiago, Region M. de Santiago, 7591047, Chile

COMPLETED

Clínica UC San Carlos de Apoquindo ( Site 4405)

Santiago, Region M. de Santiago, 7620002, Chile

RECRUITING

Anhui Provincial Hospital South District ( Site 3501)

Hefei, Anhui, 230031, China

RECRUITING

Beijing Cancer hospital-Digestive Oncology ( Site 3500)

Beijing, Beijing Municipality, 100142, China

RECRUITING

The First Affiliated Hospital of Xiamen University ( Site 3516)

Xiamen, Fujian, 361003, China

RECRUITING

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

Xinxiang, Henan, 453100, China

RECRUITING

Henan Cancer Hospital ( Site 3518)

Zhengzhou, Henan, 450008, China

RECRUITING

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

Huai'an, Jiangsu, 223300, China

RECRUITING

Shanghai Chest Hospital-Esophageal surgery department ( Site 3513)

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

Zhejiang Cancer Hospital-Thoracic oncology ( Site 3511)

Hangzhou, Zhejiang, 310022, China

RECRUITING

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

Frankfurt am Main, Hesse, 60488, Germany

COMPLETED

Universitaetsklinikum Duesseldorf ( Site 4802)

Düsseldorf, North Rhine-Westphalia, 40225, Germany

COMPLETED

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

Dresden, Saxony, 01307, Germany

RECRUITING

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

Berlin, 13353, Germany

COMPLETED

Facharztzentrum Eppendorf ( Site 4807)

Hamburg, 20249, Germany

RECRUITING

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

Meldola, Emilia-Romagna, 47014, Italy

RECRUITING

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

Milan, Lombardy, 20133, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana ( Site 3206)

Pisa, Tuscany, 56126, Italy

RECRUITING

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

Padova, Veneto, 35128, Italy

RECRUITING

Ospedale San Raffaele-Oncologia Medica ( Site 3202)

Milan, 20132, Italy

RECRUITING

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

Milan, 20141, Italy

COMPLETED

Aichi Cancer Center ( Site 3702)

Nagoya, Aichi-ken, 464-8681, Japan

RECRUITING

National Cancer Center Hospital East ( Site 3701)

Kashiwa, Chiba, 277-8577, Japan

RECRUITING

Saitama Prefectural Cancer Center ( Site 3703)

Kitaadachi-gun, Saitama, 3620806, Japan

RECRUITING

Shizuoka Cancer Center ( Site 3704)

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

RECRUITING

National Cancer Center Hospital ( Site 3700)

Chuo-ku, Tokyo, 104-0045, Japan

RECRUITING

Oslo universitetssykehus, Radiumhospitalet ( Site 4501)

Oslo, 0379, Norway

RECRUITING

National University Hospital ( Site 3800)

Singapore, South West, 119074, Singapore

RECRUITING

Asan Medical Center-Department of Oncology ( Site 3901)

Seoul, 05505, South Korea

RECRUITING

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

Seoul, 06351, South Korea

RECRUITING

Hôpitaux Universitaires de Genève (HUG) ( Site 4702)

Geneva, Canton of Geneva, 1211, Switzerland

RECRUITING

Kantonsspital Graubünden-Medizin ( Site 4700)

Chur, Kanton Graubünden, 7000, Switzerland

RECRUITING

Chang Gung Memorial Hospital at Kaohsiung ( Site 4003)

Kaohsiung Niao Sung Dist, Kaohsiung, 83301, Taiwan

RECRUITING

China Medical University Hospital ( Site 4007)

Taichung, 404332, Taiwan

RECRUITING

Taichung Veterans General Hospital-Radiation Oncology ( Site 4008)

Taichung, 407, Taiwan

RECRUITING

National Cheng Kung University Hospital ( Site 4001)

Tainan, 704, Taiwan

RECRUITING

National Taiwan University Hospital ( Site 4000)

Taipei, 10002, Taiwan

RECRUITING

Taipei Veterans General Hospital ( Site 4005)

Taipei, 112, Taiwan

RECRUITING

Chang Gung Medical Foundation-Linkou Branch ( Site 4006)

Taoyuan, 33305, Taiwan

RECRUITING

Faculty of Medicine Siriraj Hospital ( Site 4102)

Bangkoknoi, Bangkok, 10700, Thailand

RECRUITING

Chulalongkorn University ( Site 4104)

Pathumwan, Bangkok, 10330, Thailand

RECRUITING

Songklanagarind hospital ( Site 4105)

Hat Yai, Changwat Songkhla, 90110, Thailand

RECRUITING

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

Adana, 01140, Turkey (Türkiye)

RECRUITING

Hacettepe Universite Hastaneleri-oncology hospital ( Site 3402)

Ankara, 06230, Turkey (Türkiye)

COMPLETED

Memorial Ankara Hastanesi-Medical Oncology ( Site 3408)

Ankara, 06520, Turkey (Türkiye)

COMPLETED

Ankara Bilkent City Hospital-Medical Oncology ( Site 3405)

Ankara, 06800, Turkey (Türkiye)

RECRUITING

Atatürk Üniversitesi-onkoloji ( Site 3416)

Erzurum, 25070, Turkey (Türkiye)

RECRUITING

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

Istanbul, 34722, Turkey (Türkiye)

RECRUITING

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

Izmir, 35575, Turkey (Türkiye)

COMPLETED

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

Paclitaxel; Irinotecan; pembrolizumab; lenvatinib; Histamine Antagonists; Histamine H2 Antagonists; Acetaminophen; Dexamethasone

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Camptothecin; Alkaloids; Heterocyclic Compounds; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

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 1, 2022
• First Posted: April 8, 2022
• Study Start: May 16, 2023
• Primary Completion (Estimated): June 11, 2027
• Study Completion (Estimated): April 10, 2029
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

CH (2); JP (5); US (5); KR (2); SG (1); CN (8); DE (5); IT (6); NO (1); TW (7); BR (3); TH (3); TU (7); CL (4)