MSI-H Tumors, Refractory MSI - H Solid Tumors Prior of PD-(L) 1 Therapy
Conditions
Keywords
Relatlimab, Nivolumab, Immunotherapy, Anti - PD-1, Anti - LAG-3, Antibodies, MSI, MMR deficient, Microsatellite instability
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.
Interventions
DRUGNivolumab
Patients will receive treatment every 28 days for up to 2 years. Nivolumab will be administered IV on day 1 (28 day cycle).
DRUGRelatlimab
Patients will receive treatment every 28 days up to 2 years. Relatlimab will be administered IV on day 1 (28 day cycle).
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Bristol-Myers Squibb
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | 4 years |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants experiencing study drug-related toxicities | 4 years |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDung Le, MD
Johns Hopkins Medical Institution
Outcome results
None listed