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

Johns Hopkins Medicine

Status and phase: Enrolling; Phase 2

Conditions: MSI-H Tumors; Refractory MSI - H Solid Tumors Prior of PD-(L) 1 Therapy

Treatments: Drug: Nivolumab; Drug: Relatlimab

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT03607890

J18102

P50CA062924 (U.S. NIH Grant/Contract)

IRB00173534 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 42 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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42 participants in 3 patient groups

Cohort 1: Nivolumab and Relatlimab

Experimental group

Description:

480mg/160mg (co-administered)

Treatment:

Drug: Relatlimab

Drug: Nivolumab

Cohort 2: Nivolumab and Relatlimab

Experimental group

Description:

480mg/960mg or 480mg/160mg (sequential administration)

Treatment:

Drug: Relatlimab

Drug: Nivolumab

Cohort 3: Nivolumab and Relatlimab

Experimental group

Description:

480mg/480mg (sequential administration)

Treatment:

Drug: Relatlimab

Drug: Nivolumab