Study of Nivolumab and Relatlimab in Patients With Microsatellite Stable (MSS) Advanced Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT03642067
• Recruitment Status: Recruiting
• First Posted: August 22, 2018
• Last Update Posted: March 8, 2023
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information

• First Submitted Date: August 15, 2018
• First Posted Date: August 22, 2018
• Last Update Posted Date: March 8, 2023
• Actual Study Start Date: February 12, 2019
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 6, 2022)

• Cohort A/B: Objective response rate (ORR) [ Time Frame: 4 years ]
  The proportion of subjects with partial response (PR) or complete response (CR) according to RECIST 1.1.
• Cohort C: Objective response rate (ORR) [ Time Frame: 4 years ]
  The proportion of subjects with partial response (PR) or complete response (CR) according to RECIST 1.1.

Original Primary Outcome Measures (submitted: August 20, 2018)

Objective response rate (ORR) [ Time Frame: 4 years ]

The proportion of subjects with partial response (PR) or complete response (CR) according to RECIST 1.1.

Current Secondary Outcome Measures (submitted: November 22, 2019)

Number of participants experiencing study drug-related toxicities [ Time Frame: 4 years ]

Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0

Original Secondary Outcome Measures (submitted: August 20, 2018)

• Number of participants experiencing study drug-related toxicities [ Time Frame: 4 years ]
  Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0
• Overall survival (OS) [ Time Frame: 4 years ]
  Number of months from the date of first treatment until death or end of follow-up.
• Progression free survival (PFS) [ Time Frame: 4 years ]
  Number of months from treatment to disease progression (PD) or relapse from complete response (CR) as assessed using RECIST 1.1 criteria, or death due to any cause.
• Time to Progression (TTP) [ Time Frame: 4 years ]
  Number of months from the date of first treatment to the date of documented disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria).
• Disease control rate (DCR) [ Time Frame: 4 years ]
  Percentage of participants achieving stable disease (SD) or better (SD + partial response (PR) + CR).
• Best overall response (BOR) [ Time Frame: 4 years ]
  Best response recorded from the start of the treatment until disease progression/recurrence per RECIST 1.1 criteria.
• Duration of response (DOR) [ Time Frame: 4 years ]
  Number of months from the first documentation of a response to date of disease progression.
• Duration of clinical benefit (DCB) [ Time Frame: 4 years ]
  Number of months from the date of first treatment to date of disease progression in those achieving a PR or CR.
• Time to objective response (TTOR) [ Time Frame: 4 years ]
  Number of months from the date of first treatment to the date of documented partial or complete response.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Nivolumab and Relatlimab in Patients With Microsatellite Stable (MSS) Advanced Colorectal Cancer
• Official Title: Phase A Phase 2 Study Evaluating Response and Biomarkers in Patients With Microsatellite Stable (MSS) Advanced Colorectal Cancer Treated With Nivolumab in Combination With Relatlimab
• Brief Summary: The purpose of this study is to evaluate the safety and clinical activity of nivolumab and relatlimab in patients with metastatic or locally advanced microsatellite stable (MSS) colorectal cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Microsatellite Stable (MSS) Colorectal Adenocarcinomas
• Colorectal Adenocarcinoma

Intervention

• 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 Name: 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 Name: BMS-986016

Study Arms

• Experimental: Cohort A/B: Nivolumab and Relatlimab
  480mg/160mg (co-administered)
  Interventions:

  • Drug: Nivolumab
  • Drug: Relatlimab
• Experimental: Cohort C: Nivolumab and Relatlimab
  480mg/ 960mg or 480mg/480mg (sequential administration)
  Interventions:

  • Drug: Nivolumab
  • Drug: Relatlimab
• Experimental: Cohort C: Nivolumab and Relatlimab (co-administration)
  480mg/160mg (co-administration)
  Interventions:

  • Drug: Nivolumab
  • Drug: Relatlimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 5, 2020): 96
• Original Estimated Enrollment (submitted: August 20, 2018): 64
• Estimated Study Completion Date: February 2024
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥18 years.
• ECOG performance status 0 or 1
• Have metastatic or locally advanced microsatellite stable (MSS) colorectal adenocarcinoma.
• Cohort A: Primary lesion has a composite PD-L1/Mucin (CPM) score ≥ 15%.
• Cohort B: Primary lesion has a composite PD-L1/Mucin (CPM) score < 15%.
• Cohort C: Prior surgical resection of primary tumor. Prospective biomarker evaluation not required.
• Must have received at least one chemotherapy regimen.
• Patients with the presence of at least one measurable lesion using RECIST 1.1.
• Patients must have available archival tissue from the surgical resection of their primary tumor.
• Patient's acceptance of tumor biopsies.
• Life expectancy of greater than 3 months.
• Patients must have adequate organ and marrow function defined by study - specified laboratory tests.
• Documented 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. Patients with previously treated brain metastases may participate if they are stable for 4 weeks prior to beginning treatment, have no new or enlarging brain metastases, and are not using steroids for at least 1 week prior to initiation of study treatment.
• Require any antineoplastic therapy.
• History of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or anti-Lag-3 antibodies.
• Had chemotherapy, radiation, or steroids within 14 days prior to study treatment.
• Had any cytotoxic drug within 4 weeks prior to initiation of study treatment.
• Hypersensitivity reaction to any monoclonal antibody.
• Has uncontrolled intercurrent acute or chronic medical illness.
• 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.
• Requires daily supplemental oxygen.
• 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.
• Woman who are pregnant or breastfeeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Trish Brothers, RN; 410-614-3644; GIClinicalTrials@jhmi.edu

Contact: Joann Santmyer, RN; 410-614-3644; GIClinicalTrials@jhmi.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03642067
• Other Study ID Numbers: J18119; IRB00173537 ( Other Identifier: JHM IRB ); CA224-068 ( Other Identifier: other )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Original Responsible Party: Same as current
• Current Study Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Original Study Sponsor: Same as current
• Collaborators: Bristol-Myers Squibb

Investigators

• Principal Investigator: Dung Le, MD; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

• PRS Account: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Verification Date: March 2023