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

NCT04098068 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: J1365 (Cohort D)MK-3475-016NA_00085756
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

High Tumor Mutation Burden; High TMB (Tumor Mutation Burden); MSS (Microsatellite Stable)

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)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Overall Survival (OS)

  80 months

• Progression-Free Survival (PFS) in Patients Using RECIST 1.1(Response Evaluation Criteria In Solid Tumors)

  24 months

• Disease Control Rate (DCR)

  2 years

• Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity

  28 months

Study Arms (1)

MSI (Microsatellite Unstable) Negative with Mutator Phenotype

EXPERIMENTAL

Drug: MK-3475

Interventions

MK-3475 DRUG

MK-3475 (pembrolizumab) 200 mg flat dose every 21 days

Also known as: Pembrolizumab

MSI (Microsatellite Unstable) Negative with Mutator Phenotype

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Spinocerebellar Degenerations

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Dung Le, MD
• Organization: Sidney Kimmel Comprehensive Center at Johns Hopkins University

dle@jhmi.edu

443-287-0002

Study Officials

• Dung Le, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2019
• First Posted: September 20, 2019
• Study Start: January 25, 2018
• Primary Completion: May 15, 2022
• Study Completion: February 5, 2025
• Last Updated: March 30, 2025
• Results First Posted: May 19, 2023

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)