AzTrials
AzTrials

Esophageal Squamous Cell Carcinoma (ESCC)Phase 1/2NCT05342636

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

A Phase 1/2 study testing Pembrolizumab, Coformulation favezelimab/pembrolizumab and MK-4830 in people with Esophageal Squamous Cell Carcinoma (ESCC), run by Merck Sharp & Dohme LLC at 46 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab, Coformulation favezelimab/pembrolizumab and MK-4830
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
46 sitesin 13 countries
Study dates
27 Jul 2022to 5 Dec 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

46 sites in 13 countries.

46 sites in 13 countries

Turkey (Türkiye)9 sites

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

    Adana, 01140

  • Hacettepe Universite Hastaneleri-oncology hospital ( Site 1402)

    Ankara, 06230

  • Memorial Ankara Hastanesi-Medical Oncology ( Site 1408)

    Ankara, 06520

  • Ankara City Hospital-Medical Oncology ( Site 1405)

    Ankara, 06800

  • Akdeniz Universitesi Hastanesi-Medical Oncology ( Site 1410)

    Antalya, 07059

  • Atatürk Üniversitesi-onkoloji ( Site 1416)

    Erzurum, 25070

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

    Istanbul, 34722

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

    Izmir, Karsiyaka, İzmir, 009035575

  • Acibadem Altunizade Hospital-Oncology ( Site 1407)

    Üsküdar / İstanbul, Istanbul, 34662

Other trials in Turkey (Türkiye)

Taiwan7 sites

  • Chang Gung Memorial Hospital at Kaohsiung ( Site 2003)

    Kaohsiung Niao Sung Dist, Kaohsiung, 83301

  • China Medical University Hospital ( Site 2007)

    Taichung, 404332

  • Taichung Veterans General Hospital-Radiation Oncology ( Site 2008)

    Taichung, 407

  • National Cheng Kung University Hospital ( Site 2001)

    Tainan, 704

  • National Taiwan University Hospital ( Site 2000)

    Taipei, 10002

  • Taipei Veterans General Hospital ( Site 2005)

    Taipei, 112

  • Chang Gung Medical Foundation-Linkou Branch ( Site 2006)

    Taoyuan, 333

Other trials in Taiwan

Japan5 sites

  • National Cancer Center Hospital ( Site 1700)

    Chuo-ku, Tokyo, 104-0045

  • Saitama Prefectural Cancer Center ( Site 1703)

    Ina-machi, Saitama, 362-0806

  • National Cancer Center Hospital East ( Site 1701)

    Kashiwa, Chiba, 277-8577

  • Shizuoka Cancer Center ( Site 1704)

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

  • Aichi Cancer Center Hospital ( Site 1702)

    Nagoya, Aichi-ken, 464-8681

Other trials in Japan

Germany4 sites

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

    Berlin, 13353

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

    Dresden, Saxony, 01307

  • Universitaetsklinikum Duesseldorf ( Site 2802)

    Düsseldorf, North Rhine-Westphalia, 40225

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

    Frankfurt am Main, Hesse, 60488

Other trials in Germany

Italy4 sites

  • Ospedale San Raffaele-Oncologia Medica ( Site 1206)

    Milan, Lombardy, 20132

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

    Milan, Lombardy, 20133

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

    Milan, 20141

  • Istituto Oncologico Veneto IRCCS ( Site 1205)

    Padova, 35128

Other trials in Italy

Brazil3 sites

  • Liga Norte Riograndense Contra o Câncer ( Site 2303)

    Natal, Rio Grande do Norte, 59062-000

  • Hospital Nossa Senhora da Conceição ( Site 2301)

    Porto Alegre, Rio Grande do Sul, 91350-200

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

    São Paulo, São Paulo, 01246-000

Other trials in Brazil

France3 sites

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

    Brest, Finistere, 29200

  • Hopital Claude Huriez - CHU de Lille ( Site 1100)

    Lille, Nord, 59037

  • Pitie Salpetriere University Hospital ( Site 1102)

    Paris, Orne, 75013

Other trials in France

Thailand3 sites

  • Chulalongkorn University ( Site 2104)

    Bangkok, Bangkok, 10330

  • Faculty of Medicine Siriraj Hospital ( Site 2102)

    Bangkok, Bangkok, 10700

  • Songklanagarind hospital ( Site 2105)

    Hat Yai, Changwat Songkhla, 90110

Other trials in Thailand

Chile2 sites

  • FALP-UIDO ( Site 2400)

    Santiago, Region M. de Santiago, 7500921

  • Clínica las Condes ( Site 2403)

    Santiago, Region M. de Santiago, 7591047

Other trials in Chile

South Korea2 sites

  • Asan Medical Center-Department of Oncology ( Site 1901)

    Seoul, 05505

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

    Seoul, 06351

Other trials in South Korea

Switzerland2 sites

  • Kantonsspital Graubünden-Medizin ( Site 2700)

    Chur, Kanton Graubünden, 7000

  • Hôpitaux Universitaires de Genève (HUG) ( Site 2702)

    Geneva, Canton of Geneva, 1211

Other trials in Switzerland

Norway1 site

  • Oslo universitetssykehus, Radiumhospitalet ( Site 2501)

    Oslo, 0310

Other trials in Norway

Singapore1 site

  • National University Hospital ( Site 1800)

    Singapore, South West, 119074

Other trials in Singapore

About this study

Official title: 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 naïve to PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06A.

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.

Read the detailed description

The master protocol is MK-3475-U06.

Being tested
Pembrolizumab, Coformulation favezelimab/pembrolizumab, MK-4830, Lenvatinib, Irinotecan
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)
Medical subject headings
Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Also called MK-3475, KEYTRUDA®

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

  • Coformulation favezelimab/pembrolizumabBiological

    Also called MK-4280A

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

  • MK-4830Biological

    Also called anti-immunoglobulin-like transcript 4 (ILT4)

    800 mg administered via IV infusion Q3W

  • LenvatinibDrug

    Also called MK-7902, LENVIMA®

    20 mg administered via oral capsules each day

  • IrinotecanDrug

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

  • PaclitaxelDrug

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

Study groups in NCT05342636
Study groupRoleWhat they receive
Pembrolizumab plus chemotherapyExperimentalParticipants 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.
Receives: Biological: Pembrolizumab; Drug: Irinotecan; Drug: Paclitaxel
Coformulation Favezelimab/Pembrolizumab plus ChemotherapyExperimentalParticipants 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.
Receives: Biological: Coformulation favezelimab/pembrolizumab; Drug: Irinotecan; Drug: Paclitaxel
Pembrolizumab plus MK-4830 plus ChemotherapyExperimentalParticipants 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.
Receives: Biological: Pembrolizumab; Biological: MK-4830; Drug: Irinotecan; Drug: Paclitaxel
Pembrolizumab plus MK-4830 plus lenvatinibExperimentalParticipants 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.
Receives: Biological: Pembrolizumab; Biological: MK-4830; Drug: Lenvatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase

    A DLT is defined as any drug-related adverse event (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.

    Measured: Up to approximately 3 weeks

  2. Number of Participants Experiencing 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. 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.

    Measured: Up to approximately 3 Weeks

  3. Number of Participants Who Discontinue Study Treatment Due to an 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. 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.

    Measured: Up to approximately 3 weeks

  4. 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.

    Measured: Up to approximately 40 months

Secondary outcomes (5)

  1. Progression-Free Survival (PFS)

    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.

    Measured: Up to approximately 40 months

  2. Duration of Response (DOR)

    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.

    Measured: Up to approximately 40 months

  3. Overall Survival (OS)

    OS is defined as the time from the date of allocation to death from any cause.

    Measured: Up to approximately 40 months

  4. Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy 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. 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.

    Measured: Up to approximately 40 months

  5. Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy 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. 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.

    Measured: Up to approximately 104 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Apr 2022
  2. Study start27 Jul 2022
  3. Primary completion5 Dec 2025
  4. Study completion5 Dec 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05342636
Sponsor's protocol ID
3475-06A
Other IDs
2031220197, 2023-505188-36-00, U1111-1291-1899, 2021-005405-26, 2023
Status last verified
Dec 2025
First submitted
19 Apr 2022
Last updated
17 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pembrolizumab, Coformulation favezelimab/pembrolizumab and MK-4830 in people with Esophageal Squamous Cell Carcinoma (ESCC), run by Merck Sharp & Dohme LLC at 46 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in Turkey (Türkiye), Taiwan, Japan, Germany, Italy and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase (time frame: Up to approximately 3 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05342636.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in