Study of Nivolumab and Relatlimab in Advanced Mismatch Repair Deficient Cancers Resistant to Prior PD-(L)1 Inhibitor

Phase 2 Study of Nivolumab and Relatlimab in Advanced Mismatch Repair Deficient Cancers Resistant to Prior PD-(L)1 Inhibitor

The purpose of this study is to evaluate the safety and clinical activity of nivolumab and relatlimab in patients with microsatellite instability high (MSI-H) solid tumors refractory to prior PD-(L)1 therapy.

Study Overview

• Status: Recruiting
• Conditions: Refractory MSI - H Solid Tumors Prior of PD-(L) 1 Therapy; MSI-H Tumors
• Intervention / Treatment: Drug: Nivolumab; Drug: Relatlimab

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Joann Santmyer, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu
• Study Contact Backup: Name: Colleen Apostal, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • Sidney Kimmel Comprehensive Cancer Center
      • Contact: Joann Santmyer; Phone Number: 410-614-3644; Email: GIClinicaltrials@jhmi.edu
      • Contact: Trish Brothers, RN; Phone Number: 410-614-3644; Email: GIClinicaltrials@jhmi.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Have metastatic or locally advanced mismatch repair deficient/MSI-H disease.
• Patients must have received prior PD-1/PD-L1 inhibitor therapy
• Patients with the presence of at least one measurable lesion.
• Life expectancy of greater than 3 months.
• Patients must have adequate organ and marrow function defined by study - specified laboratory tests.
• Documented left ventricular ejection fraction (LVEF) ≥ 50% - 6 month prior to drug administration.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Known history or evidence of brain metastases.
• Require any antineoplastic therapy.
• History of prior treatment with anti-LAG3.
• Had chemotherapy, radiation, or steroids within 14 days prior to study treatment.
• Had any investigational cytotoxic drug within 4 weeks prior to study treatment.
• Have received any investigational drugs, a live vaccine, any allergen hyposensitization therapy, growth factors or major surgery within 28 days prior to study treatment.
• Major surgery
• Hypersensitivity reaction to any monoclonal antibody.
• Has an active known or suspected autoimmune disease.
• Has a diagnosis of immunodeficiency.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation.
• Requires daily supplemental oxygen
• History of interstitial lung disease.
• Significant heart disease
• History of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
• Infection with HIV or hepatitis B or C at screening.
• Has an active infection.
• Unable to have blood drawn.
• Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Prior life-threatening toxicity to anti-PD-1, anti-PD-L1, anti-PD-L2,or anti-CTLA4
• Woman who are pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Nivolumab and Relatlimab; 480mg/160mg (co-administered)	Drug: Nivolumab; Patients will receive treatment every 28 days for up to 2 years. Nivolumab will be administered IV on day 1 (28 day cycle).; Other Names: anti-PD-1, OPDIVO; Drug: Relatlimab; Patients will receive treatment every 28 days up to 2 years. Relatlimab will be administered IV on day 1 (28 day cycle).; Other Names: BMS-986016
Experimental: Cohort 2: Nivolumab and Relatlimab; 480mg/960mg or 480mg/160mg (sequential administration)	Drug: Nivolumab; Patients will receive treatment every 28 days for up to 2 years. Nivolumab will be administered IV on day 1 (28 day cycle).; Other Names: anti-PD-1, OPDIVO; Drug: Relatlimab; Patients will receive treatment every 28 days up to 2 years. Relatlimab will be administered IV on day 1 (28 day cycle).; Other Names: BMS-986016
Experimental: Cohort 3: Nivolumab and Relatlimab; 480mg/480mg (sequential administration)	Drug: Nivolumab; Patients will receive treatment every 28 days for up to 2 years. Nivolumab will be administered IV on day 1 (28 day cycle).; Other Names: anti-PD-1, OPDIVO; Drug: Relatlimab; Patients will receive treatment every 28 days up to 2 years. Relatlimab will be administered IV on day 1 (28 day cycle).; Other Names: BMS-986016

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants experiencing study drug-related toxicities	4 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Bristol-Myers Squibb; National Cancer Institute (NCI)
• Investigators: Principal Investigator: Dung Le, MD, Johns Hopkins Medical Institution

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2018
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Estimated): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Nivolumab; Immunotherapy; Relatlimab; Antibodies; MSI; Microsatellite instability; Anti - LAG-3; Anti - PD-1; MMR deficient
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Relatlimab
• Other Study ID Numbers: J18102; P50CA062924 (U.S. NIH Grant/Contract); IRB00173534 (Other Identifier: JHMI IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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