Evaluating nivolumab and relatlimab for advanced cancers resistant to prior therapy

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

This study is testing if two immunotherapy drugs, nivolumab and relatlimab, can help adults with advanced cancers that didn't get better with previous treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Academic / other)
• Drugs / interventions: chemotherapy, radiation, nivolumab, relatlimab
• Locations: 2 sites (Los Angeles, California and 1 other locations)
• Trial ID: NCT03607890 on ClinicalTrials.gov

What this trial studies

This study aims to assess the safety and effectiveness of nivolumab and relatlimab in patients with advanced mismatch repair deficient cancers that have not responded to previous PD-(L)1 inhibitor treatments. Participants must be adults with measurable MSI-H solid tumors and a performance status of 0 or 1. The study will involve administering these immunotherapy agents to determine their clinical activity in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced mismatch repair deficient/MSI-H solid tumors who have previously received PD-1/PD-L1 therapy.

Not a fit: Patients with known brain metastases or those requiring other antineoplastic therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with refractory MSI-H tumors.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, suggesting potential for success in this trial.

Eligibility criteria

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.

Where this trial is running

Los Angeles, California and 1 other locations

• Cedars Sinai Medical Center — Los Angeles, California, United States (Recruiting)
• Sidney Kimmel Comprehensive Cancer Center — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Dung Le, MD — Johns Hopkins Medical Institution
• Study coordinator: Colleen Apostal, RN

Conditions Refractory MSI - H Solid Tumors Prior of PD- 1 Therapy; MSI-H Tumors; Relatlimab; Nivolumab; Immunotherapy; Anti - PD-1; Anti - LAG-3; Antibodies