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

Phase 2
Recruiting
Conditions
MSI-H Tumors
Refractory MSI - H Solid Tumors Prior of PD-(L) 1 Therapy
Interventions
Registration Number
NCT03607890
Lead Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
42
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 3: Nivolumab and RelatlimabNivolumab480mg/480mg (sequential administration)
Cohort 1: Nivolumab and RelatlimabNivolumab480mg/160mg (co-administered)
Cohort 2: Nivolumab and RelatlimabNivolumab480mg/960mg or 480mg/160mg (sequential administration)
Cohort 1: Nivolumab and RelatlimabRelatlimab480mg/160mg (co-administered)
Cohort 2: Nivolumab and RelatlimabRelatlimab480mg/960mg or 480mg/160mg (sequential administration)
Cohort 3: Nivolumab and RelatlimabRelatlimab480mg/480mg (sequential administration)
Primary Outcome Measures
NameTimeMethod
Objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)4 years
Secondary Outcome Measures
NameTimeMethod
Number of participants experiencing study drug-related toxicities4 years

Trial Locations

Locations (2)

Sidney Kimmel Comprehensive Cancer Center

🇺🇸

Baltimore, Maryland, United States

Cedars Sinai Medical Center

🇺🇸

Los Angeles, California, United States

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