Clinical trial NCT03607890: Study of Nivolumab and Relatlimab in Advanced Mismatch Repair Deficient Cancers Resistant to Prior PD-(L)1 Inhibitor
Official title: Phase 2 Study of Nivolumab and Relatlimab in Advanced Mismatch Repair Deficient Cancers Resistant to Prior PD-(L)1 Inhibitor
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Refractory MSI - H Solid Tumors Prior of PD-(L) 1 Therapy
MSI-H Tumors
Keywords: Relatlimab
Nivolumab
Immunotherapy
Anti - PD-1
Anti - LAG-3
Antibodies
MSI
MMR deficient
Microsatellite instability
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: National Cancer Institute (NCI)
First posted: 2018-07-31
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
timeFrame: 4 years
Secondary outcomes:
measure: Number of participants experiencing study drug-related toxicities
timeFrame: 4 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Johns Hopkins Medical Institution
name: Dung Le, MD
role: PRINCIPAL_INVESTIGATOR
References: