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Completed

NCT Number: NCT05342636

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

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.

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Key information

Conditions

Esophageal Squamous Cell Carcinoma (ESCC) Carcinoma Carcinoma, Squamous Cell Digestive System Diseases Digestive System Neoplasms Esophageal Diseases Esophageal Neoplasms Esophageal Squamous Cell Carcinoma Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplasms, Squamous Cell Parkinson Disease 4, Autosomal Dominant Lewy Body

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Liga Norte Riograndense Contra o Câncer ( Site 2303), Natal, Rio Grande do Norte, Brazil

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About this study

The master protocol is MK-3475-U06.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.
  • 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 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
  • 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

Treatment and study plan

Pembrolizumab

Biological

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

Other names: MK-3475, KEYTRUDA®

Coformulation favezelimab/pembrolizumab

Biological

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

Other names: MK-4280A

MK-4830

Biological

800 mg administered via IV infusion Q3W

Other names: anti-immunoglobulin-like transcript 4 (ILT4)

Lenvatinib

Drug

20 mg administered via oral capsules each day

Other names: MK-7902, LENVIMA®

Irinotecan

Drug

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

paclitaxel

Drug

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

Primary outcomes

  1. Number of Participants Experiencing 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 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.

  2. Number of Participants Experiencing an Adverse Event (AE) 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. 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.

  3. 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 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.

  4. Objective Response Rate (ORR)

    Time frame: Up to approximately 40 months

    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.

Secondary outcomes

  1. Progression-Free Survival (PFS)

    Time frame: Up to approximately 40 months

    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.

  2. Duration of Response (DOR)

    Time frame: Up to approximately 40 months

    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.

  3. Overall Survival (OS)

    Time frame: Up to approximately 40 months

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

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

    Time frame: Up to approximately 40 months

    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.

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

    Time frame: Up to approximately 104 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.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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.

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Apr 22, 2022
Registry last updated
Dec 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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