A Phase II Two-Arm Open-Label Study of Nivolumab Plus Relatlimab or Ipilimumab in Metastatic Melanoma Stratified by MHC-II Expression
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Metastatic Melanoma
- Sponsor
- Elizabeth Davis
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Change in Activated GZMB+ CD8+T-cell Density Intratumorally, of Two Immunotherapy Regimens
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
This is an open-label, non-randomized two arm Phase 2 study of intravenous nivolumab plus intravenous ipilimumab or intravenous relatlimab in patients with metastatic melanoma stratified by MHC-II expression.
Detailed Description
Primary Objective: • To evaluate the efficacy, measured by change in activated GZMB+ CD8+ T-cell density intratumorally, of two immunotherapy regimens in patients with advanced melanoma: * nivolumab plus relatlimab in patients with MHC-II (+) melanoma, and * nivolumab plus ipilimumab in patients with MHC-II (-) melanoma. Secondary Objectives: • To evaluate the response rate, median progression free survival, overall survival, and safety and tolerability of nivolumab plus relatlimab in patients with MHC-II (+) melanoma, and of nivolumab plus ipilimumab in patients with MHC-II (-) melanoma. Exploratory Objectives * To explore potential associations of biomarkers with clinical efficacy and/or incidence of adverse events due to study drug by analyzing biomarker measures within the peripheral blood and tumor microenvironment.
Investigators
Elizabeth Davis
Sponsor Investigator
Vanderbilt-Ingram Cancer Center
Eligibility Criteria
Inclusion Criteria
- •Signed and dated written informed consent.
- •≥ 18 years of age at the time of informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Histologically confirmed locally advanced/unresectable or metastatic melanoma.
- •Patients who have received prior anti-CTLA-4 or anti-PD-1/PD-L1 for adjuvant treatment of melanoma are eligible if \> 6 months have elapsed between the last dose of adjuvant treatment and starting this study - provided there is no history of life-threatening toxicity related to such prior treatment, or such toxicity is unlikely to re-occur with standard countermeasures (e.g. hormone replacement after endocrinopathy).
- •Patients who have received adjuvant therapy with interferon and/or a BRAF inhibitor and/or MEK inhibitor for adjuvant therapy are permitted to enroll.
- •At least one measureable target lesion as defined by RECIST 1.1 which can be followed byCT or MRI.
- •If located in a previously irradiated area, a tumor lesion is considered a measurable/target lesion only if subsequent disease progression in the lesion has been documented at least 90 days following completion of radiotherapy.
- •Adequate organ and bone marrow function ≤ 14 days prior to first dose of protocol-indicated treatment:
- •White blood cell count (WBC) ≥ 2,000/mm3
Exclusion Criteria
- •Patients with uveal melanoma.
- •Prior systemic anticancer therapy for unresectable or metastatic melanoma.
- •Prior treatment with LAG-3 targeted agents.
- •Subjects with active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- •Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
- •Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent.
- •Uncontrolled angina within the 3 months prior to consent.
- •Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes, or poorly controlled atrial fibrillation).
- •QTc prolongation \> 480 msec.
- •History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled deep venous thrombosis, etc).
Arms & Interventions
Arm A
Nivolumab and Relatlimab
Intervention: Nivolumab
Arm A
Nivolumab and Relatlimab
Intervention: Relatlimab
Arm B
Nivolumab and Ipilimumab
Intervention: Nivolumab
Arm B
Nivolumab and Ipilimumab
Intervention: Ipilimumab
Outcomes
Primary Outcomes
Change in Activated GZMB+ CD8+T-cell Density Intratumorally, of Two Immunotherapy Regimens
Time Frame: Approximately 16 months
Secondary Outcomes
- Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 5.0(Up to 30 days from last dose of drugs (average of 13 cycles))
- Response Rate(Approximately 16 months)
- Median Overall Survival(Approximately 16 months)
- Median Progression Free Survival(Approximately 16 months)