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
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Immunocore Ltd
- Enrollment
- 680
- Locations
- 374
- Primary Endpoint
- Progression-Free Survival (PFS)
Study Overview
Brief Summary
This is a phase 3, randomized, controlled study of brenetafusp (IMC-F106C) plus nivolumab compared to standard nivolumab regimens in HLA-A*02:01-positive participants with previously untreated advanced melanoma.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Arm A: Brenetafusp Low Dose + Nivolumab
Participants receive brenetafusp Low Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W.
Closed to randomization after dose recommendation by the IDMC in November 2025.
Intervention: Brenetafusp (Drug)
Arm A: Brenetafusp Low Dose + Nivolumab
Participants receive brenetafusp Low Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W.
Closed to randomization after dose recommendation by the IDMC in November 2025.
Intervention: Nivolumab (Drug)
Arm B: Brenetafusp High Dose + Nivolumab
Participants receive brenetafusp High Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W.
Selected as go-forward experimental arm after dose recommendation by the IDMC in November 2025
Intervention: Brenetafusp (Drug)
Arm B: Brenetafusp High Dose + Nivolumab
Participants receive brenetafusp High Dose once weekly (QW) for the first 13 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W). Nivolumab is given Q4W.
Selected as go-forward experimental arm after dose recommendation by the IDMC in November 2025
Intervention: Nivolumab (Drug)
Arm C: Nivolumab OR Nivolumab + Relatlimab
Participants receive nivolumab 480 mg monotherapy, or nivolumab 480 mg + relatlimab 160 mg, Q4W.
Intervention: Nivolumab (Drug)
Arm C: Nivolumab OR Nivolumab + Relatlimab
Participants receive nivolumab 480 mg monotherapy, or nivolumab 480 mg + relatlimab 160 mg, Q4W.
Intervention: Nivolumab + Relatlimab (Drug)
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: Up to ~45 months
PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
Secondary Outcomes
- Number of Participants Experiencing a Dose Interruption, Reduction, or Discontinuation(Up to ~45 months)
- Maximum Plasma Concentration (Cmax) of IMC-F106C(Day 1 of Weeks 1, 2, and 3: Predose and 0.5 and 4 hours postdose)
- Incidence of anti-IMC-F106C Antibodies(Up to ~45 months)
- Association between PFS and Intra-Tumor Immune Cells(Up to ~45 months)
- Health-Related Quality of Life(Up to ~45 months)
- Overall Survival (OS)(Up to ~57 months)
- Overall Response Rate (ORR)(Up to ~45 months)
- Number of Participants Experiencing ≥1 Adverse Event (AE)(Up to ~57 months)
- Number of Participants Experiencing ≥1 Serious Adverse Event (SAE)(Up to ~57 months)