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

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins3 sites in 1 country12 target enrollmentJanuary 25, 2018

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

InterventionsMK-3475

DrugsMK-3475

Overview

Phase: Phase 2
Intervention: MK-3475
Conditions: High Tumor Mutation Burden
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Enrollment: 12
Locations: 3
Primary Endpoint: Objective Response Rate (ORR) in Patients With MSI (Microsatellite Unstable)-Negative Solid Tumor Malignancies With a Mutator Phenotype
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

January 25, 2018

End Date

February 5, 2025

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Responsible Party

Sponsor

Eligibility Criteria

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

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.

Arms & Interventions

MSI (Microsatellite Unstable) Negative with Mutator Phenotype

Intervention: MK-3475

Outcomes

Primary Outcomes

Objective Response Rate (ORR) in Patients With MSI (Microsatellite Unstable)-Negative Solid Tumor Malignancies With a Mutator Phenotype

Time Frame: 2 years

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.

Secondary Outcomes

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)