IMC-F106C Regimen Versus Nivolumab Regimens in Previously Untreated Advanced Melanoma (PRISM-MEL-301)

Study Overview
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Brief Summary
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This is a phase 3, randomized, controlled study of IMC-F106C plus nivolumab compared to standard nivolumab regimens in HLA-A*02:01-positive participants with previously untreated advanced melanoma.

Official Title
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A Phase 3 Randomized, Controlled Study of IMC-F106C Plus Nivolumab Versus Nivolumab Regimens in HLA-A*02:01-Positive Participants With Previously Untreated Advanced Melanoma (PRISM-MEL-301

Conditions
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Advanced Melanoma

Intervention / Treatment
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* Biological: IMC-F106C
* Biological: Nivolumab
* Biological: Nivolumab + Relatlimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be HLA-A*02:01-positive Participants must have histologically confirmed Stage IV or unresectable Stage III melanoma Archived or fresh tumor tissue sample that must be confirmed as adequate Participants must have measurable disease per RECIST 1.1 Participant must have BRAF V600 mutation status determined Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the study screening date until 5 months after the final dose of study intervention Exclusion Criteria: Participants with a history of a malignant disease other than those being treated in this study Participants with untreated, active, or symptomatic central nervous system (CNS) metastases or carcinomatous meningitis Hypersensitivity to IMC-F106C, nivolumab, relatlimab, or any associated excipients Participants with clinically significant pulmonary disease or impaired lung function Participants with clinically significant cardiac disease or impaired cardiac function Participants with active autoimmune disease requiring immunosuppressive treatment Participants with any medical condition that is poorly controlled or that would, in the Investigator's or Sponsor's judgment, adversely impact the participant's participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results Participants who received prior systemic anticancer therapy for unresectable or metastatic melanoma Participants with a history of a life-threatening AE related to prior anti-PD-(L)1 or anti-LAG-3

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: IMC-F106C Low Dose + Nivolumab<br>Participants receive IMC-F106C Low Dose once weekly (QW) for the first 12 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W) until Week 101. Nivolumab is given Q4W until Week 101. | Biological: IMC-F106C<br>* Soluble PRAME-specific T cell receptor with anti-CD3 scFV concentrate for solution for intravenous (IV) infusion at a unit dose of 0.2 mg/mL.<br>Biological: Nivolumab<br>* Concentrate for solution for infusion at a unit dose of 10 mg/mL.<br>* Other names: OPDIVO;|
| Experimental: Arm B: IMC-F106C High Dose + Nivolumab<br>Participants receive IMC-F106C High Dose QW for the first 12 weeks, then Q2W through Week 51, and then Q4W until Week 101. Nivolumab is given Q4W until Week 101. | Biological: IMC-F106C<br>* Soluble PRAME-specific T cell receptor with anti-CD3 scFV concentrate for solution for intravenous (IV) infusion at a unit dose of 0.2 mg/mL.<br>Biological: Nivolumab<br>* Concentrate for solution for infusion at a unit dose of 10 mg/mL.<br>* Other names: OPDIVO;|
| Active Comparator: Arm C: Nivolumab OR Nivolumab + Relatlimab<br>Participants receive nivolumab 480 mg monotherapy, or nivolumab 480 mg + relatlimab 160 mg, Q4W until Week 101. | Biological: Nivolumab<br>* Concentrate for solution for infusion at a unit dose of 10 mg/mL.<br>* Other names: OPDIVO;Biological: Nivolumab + Relatlimab<br>* Concentrate for solution for infusion at a unit dose of 10 mg/mL.<br>* Other names: OPDUALAG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1). | Up to  24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is the time from randomization to time of death from any cause. | Up to  24 months | 
| Overall Response Rate (ORR) | ORR as assessed by BICR according to RECIST 1.1. | Up to  24 months | 
| Number of Participants Experiencing ≥1 Adverse Event (AE) | An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur in the study. | Up to  36 months | 
| Number of Participants Experiencing ≥1 Serious Adverse Event (SAE) | An SAE is any untoward medical consequence that results in death; requires inpatient hospitalization or prolongs existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or any other important medical event in the opinion of the Investigator. | Up to  36 months | 
| Number of Participants Experiencing a Dose Interruption, Reduction, or Discontinuation | The number of participants with a dose interruption, reduction, or discontinuation due to AE will be reported. | Up to  24 months | 
| Maximum Plasma Concentration (Cmax) of IMC-F106C | The Cmax of IMC-F106C will be reported. | Day 1 of Weeks 1, 2, and 3: Predose and 0.5 and 4 hours postdose | 
| Incidence of anti-IMC-F106C Antibodies | The incidence of anti-IMC-F106C antibodies, including neutralizing antibodies, will be reported. | Up to  24 months | 
| Association between PFS and Intra-Tumor Immune Cells | The potential association between the effect of IMC-F106C on efficacy and intra-tumor environment will be explored. Intra-tumor environment is estimated as the ratio of CD3+ to CD163+ cells and the correlation with PFS will be estimated by the hazard ratio (+/- 95% CI) from a Cox model. This analysis will be restricted to subjects randomized to receive IMC-F106C. | Up to  24 months |