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)

April 19, 2024 updated by: Merck Sharp & Dohme LLC

A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer Previously Exposed to PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06B

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.

Study Overview

Status

Recruiting

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
    • Rio Grande Do Norte
      • Natal, Rio Grande Do Norte, Brazil, 59062-000
        • Recruiting
        • Liga Norte Riograndense Contra o Câncer ( Site 4303)
        • Contact:
          • Study Coordinator
          • Phone Number: 55 84 991191032
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brazil, 91350-200
        • Recruiting
        • Hospital Nossa Senhora da Conceição ( Site 4301)
        • Contact:
          • Study Coordinator
          • Phone Number: +5551993590437
    • Sao Paulo
      • São Paulo, Sao Paulo, Brazil, 01246-000
        • Recruiting
        • ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 4300)
        • Contact:
          • Study Coordinator
          • Phone Number: 5511993103312
  • Chile
    • Region M. De Santiago
      • Santiago, Region M. De Santiago, Chile, 7500921
        • Recruiting
        • FALP-UIDO ( Site 4400)
        • Contact:
          • Study Coordinator
          • Phone Number: 56224457254
      • Santiago, Region M. De Santiago, Chile, 7591047
        • Completed
        • Clínica las Condes ( Site 4403)
  • China
    • Anhui
      • Hefei, Anhui, China, 230036
        • Recruiting
        • Anhui Provincil Hospital South District ( Site 3501)
        • Contact:
          • Study Coordinator
          • Phone Number: 13955195511
    • Beijing
      • Beijing, Beijing, China, 100142
        • Recruiting
        • Beijing Cancer hospital-Digestive Oncology ( Site 3500)
        • Contact:
          • Study Coordinator
          • Phone Number: 010-88121122
    • Henan
      • Xinxiang, Henan, China, 453100
        • Recruiting
        • The First Affiliated Hospital of Xinxiang Medical University-Oncology ( Site 3510)
        • Contact:
          • Study Coordinator
          • Phone Number: 8613663030446
    • Jiangsu
      • Huai'an, Jiangsu, China, 223300
        • Recruiting
        • First Huai'an Hospital Affiliated to Nanjing Medical University ( Site 3506)
        • Contact:
          • Study Coordinator
          • Phone Number: 8613861597105
    • Shanghai
      • Shanghai, Shanghai, China, 200030
        • Recruiting
        • Shanghai Chest Hospital-Esophageal surgery department ( Site 3513)
        • Contact:
          • Study Coordinator
          • Phone Number: +86 21 22200000
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310022
        • Recruiting
        • Zhejiang Cancer Hospital-Thoracic oncology ( Site 3511)
        • Contact:
          • Study Coordinator
          • Phone Number: 86 13858182310
  • Germany
      • Berlin, Germany, 13353
        • Recruiting
        • Charité Campus Virchow-Klinikum-Klinik Hämatologie Onkologie Tumorimmunologie ( Site 4804)
        • Contact:
          • Study Coordinator
          • Phone Number: +4930450657306
    • Hessen
      • Frankfurt, Hessen, Germany, 60488
        • Recruiting
        • Institut für Klinisch Onkologische Forschung-Klink für Onkologie und Hämatologie ( Site 4801)
        • Contact:
          • Study Coordinator
          • Phone Number: 496976014187
  • Italy
      • Milano, Italy, 20141
        • Completed
        • Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative (
    • Lombardia
      • Milan, Lombardia, Italy, 20133
        • Recruiting
        • Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 3200)
        • Contact:
          • Study Coordinator
          • Phone Number: 390223903835
      • Milano, Lombardia, Italy, 20132
        • Recruiting
        • Ospedale San Raffaele-Oncologia Medica ( Site 3202)
        • Contact:
          • Study Coordinator
          • Phone Number: +393400005069
  • Japan
    • Aichi
      • Nagoya, Aichi, Japan, 464-8681
        • Recruiting
        • Aichi Cancer Center Hospital ( Site 3702)
        • Contact:
          • Study Coordinator
          • Phone Number: +81-52-762-6111
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • Recruiting
        • National Cancer Center Hospital East ( Site 3701)
        • Contact:
          • Study Coordinator
          • Phone Number: +81-4-7133-1111
    • Saitama
      • Ina-machi, Saitama, Japan, 362-0806
        • Recruiting
        • Saitama Prefectural Cancer Center ( Site 3703)
        • Contact:
          • Study Coordinator
          • Phone Number: +81-48-722-1111
    • Shizuoka
      • Nagaizumi-cho,Sunto-gun, Shizuoka, Japan, 411-8777
        • Recruiting
        • Shizuoka Cancer Center ( Site 3704)
        • Contact:
          • Study Coordinator
          • Phone Number: +81-55-989-5222
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • Recruiting
        • National Cancer Center Hospital ( Site 3700)
        • Contact:
          • Study Coordinator
          • Phone Number: +81-3-3542-2511
  • Korea, Republic of
      • Seoul, Korea, Republic of, 05505
        • Recruiting
        • Asan Medical Center-Department of Oncology ( Site 3901)
        • Contact:
          • Study Coordinator
          • Phone Number: +82230107179
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Samsung Medical Center-Division of Hematology/Oncology ( Site 3900)
        • Contact:
          • Study Coordinator
          • Phone Number: +82234106518
  • Norway
      • Oslo, Norway, 0310
        • Recruiting
        • Oslo universitetssykehus, Radiumhospitalet ( Site 4501)
        • Contact:
          • Study Coordinator
          • Phone Number: 4723026600
  • Singapore
    • South West
      • Singapore, South West, Singapore, 119074
        • Recruiting
        • National University Hospital ( Site 3800)
        • Contact:
          • Study Coordinator
          • Phone Number: +65 6779 5555
  • Switzerland
    • Geneve
      • Genève, Geneve, Switzerland, 1211
        • Recruiting
        • Hôpitaux Universitaires de Genève (HUG) ( Site 4702)
        • Contact:
          • Study Coordinator
          • Phone Number: 41223729861
    • Grisons
      • Chur, Grisons, Switzerland, 7000
        • Recruiting
        • Kantonsspital Graubünden-Medizin ( Site 4700)
        • Contact:
          • Study Coordinator
          • Phone Number: 41812566884
  • Taiwan
      • Taichung, Taiwan, 404332
        • Recruiting
        • China Medical University Hospital ( Site 4007)
        • Contact:
          • Study Coordinator
          • Phone Number: +886975680932
      • Taichung, Taiwan, 407
        • Recruiting
        • Taichung Veterans General Hospital-Radiation Oncology ( Site 4008)
        • Contact:
          • Study Coordinator
          • Phone Number: 8864235925255613
      • Tainan, Taiwan, 704
        • Recruiting
        • National Cheng Kung University Hospital ( Site 4001)
        • Contact:
          • Study Coordinator
          • Phone Number: +886972401107
      • Taipei, Taiwan, 112
        • Recruiting
        • Taipei Veterans General Hospital ( Site 4005)
        • Contact:
          • Study Coordinator
          • Phone Number: +8862287121212573
      • Taipei, Taiwan, 100225
        • Recruiting
        • National Taiwan University Hospital ( Site 4000)
        • Contact:
          • Study Coordinator
          • Phone Number: +886223123456
      • Taoyuan, Taiwan, 333
        • Recruiting
        • Chang Gung Medical Foundation-Linkou Branch ( Site 4006)
        • Contact:
          • Study Coordinator
          • Phone Number: +88633281200
    • Kaohsiung
      • Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan, 83301
        • Recruiting
        • Chang Gung Memorial Hospital at Kaohsiung ( Site 4003)
        • Contact:
          • Study Coordinator
          • Phone Number: 886773171233267
  • Thailand
    • Krung Thep Maha Nakhon
      • Bangkok, Krung Thep Maha Nakhon, Thailand, 10700
        • Recruiting
        • Faculty of Medicine Siriraj Hospital ( Site 4102)
        • Contact:
          • Study Coordinator
          • Phone Number: +6624194488
  • Turkey
      • Ankara, Turkey, 06230
        • Recruiting
        • Hacettepe Universite Hastaneleri-oncology hospital ( Site 3402)
        • Contact:
          • Study Coordinator
          • Phone Number: +903123052910
      • Ankara, Turkey, 06800
        • Recruiting
        • Ankara Bilkent City Hospital-Medical Oncology ( Site 3405)
        • Contact:
          • Study Coordinator
          • Phone Number: 905555306271
      • Erzurum, Turkey, 25070
        • Recruiting
        • Atatürk Üniversitesi-onkoloji ( Site 3416)
        • Contact:
          • Study Coordinator
          • Phone Number: 905072864555
      • Istanbul, Turkey, 34722
        • Recruiting
        • TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 3403)
        • Contact:
          • Study Coordinator
          • Phone Number: 00905063509061

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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-PD1/PD-L1 based 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 history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.
  • Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease.
  • Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
  • 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.
  • Known GI malabsorption or any other condition that may affect the absorption of lenvatinib. (Not applicable to actively enrolling arms as of Amendment 5)
  • Has risk for significant 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. (Not applicable to actively enrolling arms as of Amendment 5)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: Paclitaxel
80-100 mg/m2 IV infusion, administered on days 1, 8, and 15 of every 28-day cycle.
Drug: Irinotecan
180 mg/m2 IV infusion, administered on day 1 of every 14-day cycle.
Experimental: 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.
Drug: Paclitaxel
80-100 mg/m2 IV infusion, administered on days 1, 8, and 15 of every 28-day cycle.
Drug: Irinotecan
180 mg/m2 IV infusion, administered on day 1 of every 14-day cycle.
Biological: Pembrolizumab
200 mg IV infusion, administered every Q3W.
Other Names:
  • MK-3475
  • KEYTRUDA®
Biological: MK-4830
800 mg IV infusion, administered Q3W up to 35 infusions.
Other Names:
  • anti-immunoglobulin-like transcript 4 (anti-ILT4)
Experimental: 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.
Biological: Pembrolizumab
200 mg IV infusion, administered every Q3W.
Other Names:
  • MK-3475
  • KEYTRUDA®
Biological: MK-4830
800 mg IV infusion, administered Q3W up to 35 infusions.
Other Names:
  • anti-immunoglobulin-like transcript 4 (anti-ILT4)
Drug: Lenvatinib
20 mg oral administration every day.
Other Names:
  • MK-7902
  • LENVIMA®
Experimental: Sacituzumab tirumotecan
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.
Drug: Antihistamine
Administered per product label.
Drug: H2 Receptor Antagonist
Administered per product label.
Drug: Acetaminophen (or equivalent)
Administered per product label.
Drug: Dexamethasone (or equivalent)
Administered per product label.
Biological: Sacituzumab tirumotecan
4 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.
Other Names:
  • SKB264
  • MK-2870

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During Safety Lead-in Phase
Time Frame: Up to approximately 3 weeks
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 Experiencing Adverse Events (AEs) During Safety Lead-in Phase
Time Frame: Up to approximately 3 weeks
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
Time Frame: Up to approximately 3 weeks
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)
Time Frame: Up to approximately 92 weeks
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 92 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Up to approximately 189 weeks
PFS is defined as the time from allocation to the first documented progressive disease (PD) as assessed by RECIST 1.1 or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.
Up to approximately 189 weeks
Duration of Response (DOR)
Time Frame: Up to approximately 189 weeks
For participants who demonstrate a confirmed 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 RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.
Up to approximately 189 weeks
Overall Survival (OS)
Time Frame: Up to approximately 189 weeks
OS is defined as the time from the date of allocation to death from any cause.
Up to approximately 189 weeks
Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase
Time Frame: Up to approximately 189 weeks
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 189 weeks
Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase
Time Frame: Up to approximately 189 weeks
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 189 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 16, 2023

Primary Completion (Estimated)

November 7, 2026

Study Completion (Estimated)

September 20, 2028

Study Registration Dates

First Submitted

April 1, 2022

First Submitted That Met QC Criteria

April 1, 2022

First Posted (Actual)

April 8, 2022

Study Record Updates

Last Update Posted (Actual)

April 22, 2024

Last Update Submitted That Met QC Criteria

April 19, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-06B
  • 2021-005443-76 (EudraCT Number)
  • jRCT2031220582 (Registry Identifier: Japan Registry of Clinical Trials (jRCT))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Esophageal Squamous Cell Carcinoma

Clinical Trials on Paclitaxel

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Saint Lucia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe