RECRUITING

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)

Conditions

Esophageal Squamous Cell Carcinoma 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)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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 Previously Exposed to PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06B

Quick Facts

Study Start:2023-05-16

Study Completion:2028-09-20

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05319730

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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. * Participants with human immunodeficiency virus (HIV) with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. * Concurrent active hepatitis B and 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)

Inclusion Criteria

Exclusion 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.

* 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.
* Participants with human immunodeficiency virus (HIV) with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Concurrent active hepatitis B and 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)

Contacts and Locations

Study Contact

Toll Free Number

CONTACT

1-888-577-8839

Trialsites@msd.com

Principal Investigator

Medical Director

STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Study Locations (Sites)

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

East Syracuse, New York, 13057

United States

Collaborators and Investigators

Sponsor: Merck Sharp & Dohme LLC

Medical Director, STUDY_DIRECTOR, Merck Sharp & Dohme LLC

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 Registration Dates

Study Start Date2023-05-16

Study Completion Date2028-09-20

Study Record Updates

Study Start Date2023-05-16

Study Completion Date2028-09-20

Terms related to this study

Keywords Provided by Researchers

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)

Additional Relevant MeSH Terms

Esophageal Squamous Cell Carcinoma