Study of MK-3475 (Pembrolizumab) in Patients With Microsatellite Unstable (MSI) Tumors (Cohort D)

Phase 2 Study of MK-3475 (Pembrolizumab) in Patients With Microsatellite Unstable (MSI) Tumors

This study will be looking at whether MK-3475 (pembrolizumab) is effective (anti-tumor activity) and safe in patients with MSI (Microsatellite Unstable) negative cancer with a mutator phenotype.

Study Overview

• Status: Completed
• Conditions: High Tumor Mutation Burden; High TMB (Tumor Mutation Burden); MSS (Microsatellite Stable)
• Intervention / Treatment: Drug: MK-3475

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with microsatellite stable tumor and a tumor mutation burden (TMB) level measured at > 20 mutations per megabase pairs (MB)
• Have measurable disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
• Adequate organ function as defined by study-specified laboratory tests
• Must use acceptable form of birth control through the study and for 28 days after final dose of study drug
• Signed informed consent form
• Willing and able to comply with study procedures
• Agree to have a biopsy of their cancer
• Patients with colon cancer must have received at least two prior cancer therapy regimens.
• Patients with other cancer types must have received at least one prior cancer therapy
• Progressive disease

Exclusion Criteria:

• Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements.
• Patients who have had chemotherapy or biological cancer therapy within 2 weeks prior to the first dose of study drug
• Patients who have had radiation within 2 weeks prior to the first dose of study drug
• Patients who have undergone major surgery within 4 weeks of dosing of investigational agent
• Patients who have received another investigational product or investigational device within 4 weeks prior to receiving study drug
• Patients who have received any of the following concomitant therapy: Interleukin-2 (IL-2), interferon, or other non-study immunotherapy regimens, immunosuppressive agents, other investigational therapies or chronic use of systemic corticosteroids within one week prior to first dose of study drug
• Patients who have received a live vaccine within 4 weeks prior to or after any dose of MK-3475 (exception: inactivated flu vaccines)
• Patients who have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration
• Patient who have had prior treatment with anti-PD-1 (anti-programmed cell death protein 1), anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies
• Patients with history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis, central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin.
• Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
• Patients with evidence of interstitial lung disease
• Systemically active steroid use
• Patients on home oxygen
• Patients with oxygen saturation of <92% on room air by pulse oximetry
• Pregnant or lactating
• Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
• Patient with known active central nervous system metastases and/or carcinomatous meningitis.
• Patients with primary brain tumors.
• Requires any other form of systemic or localized antineoplastic therapy while on study
• Has any tissue or organ allograft
• Patients with history of allogeneic hematopoeitic stem cell transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSI (Microsatellite Unstable) Negative with Mutator Phenotype	Drug: MK-3475; MK-3475 (pembrolizumab) 200 mg flat dose every 21 days; Other Names: Pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) in Patients With MSI (Microsatellite Unstable)-Negative Solid Tumor Malignancies With a Mutator Phenotype	Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity	When calculating the incidence of AEs, each adverse event (AE) (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.	28 months
Disease Control Rate (DCR)	Disease Control Rate (DCR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.	2 years
Overall Survival (OS)	OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.	80 months
Progression-Free Survival (PFS) in Patients Using RECIST 1.1(Response Evaluation Criteria In Solid Tumors)	PFS is defined as the number of months from the date of first dose to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.	24 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Dung Le, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2018
• Primary Completion (Actual): May 15, 2022
• Study Completion (Actual): February 5, 2025

Study Registration Dates

• First Submitted: September 19, 2019
• First Submitted That Met QC Criteria: September 19, 2019
• First Posted (Actual): September 20, 2019

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 13, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Mutation load; Tumor mutation load; Mutation burden; Tumor mutation burden (TMB); Hypermutation; MSI Negative with Mutator Phenotype (High Tumor Mutation Burden); TMB (Tumor Mutation Burden)
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: J1365 (Cohort D); MK-3475-016 (Other Identifier: Merck); NA_00085756 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No