IMC-F106C Regimen Versus Nivolumab Regimens in Previously Untreated Advanced Melanoma (PRISM-MEL-301)
- Conditions
- Advanced Melanoma
- Interventions
- Registration Number
- NCT06112314
- Lead Sponsor
- Immunocore Ltd
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 680
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Brenetafusp Low Dose + Nivolumab Brenetafusp 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. Arm A: Brenetafusp Low Dose + Nivolumab 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. Arm B: Brenetafusp High Dose + Nivolumab Brenetafusp 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. Arm B: Brenetafusp High Dose + Nivolumab 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. Arm C: Nivolumab OR Nivolumab + Relatlimab Nivolumab Participants receive nivolumab 480 mg monotherapy, or nivolumab 480 mg + relatlimab 160 mg, Q4W. Arm C: Nivolumab OR Nivolumab + Relatlimab Nivolumab + Relatlimab Participants receive nivolumab 480 mg monotherapy, or nivolumab 480 mg + relatlimab 160 mg, Q4W.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) 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 Outcome Measures
Name Time Method Maximum Plasma Concentration (Cmax) of IMC-F106C Day 1 of Weeks 1, 2, and 3: Predose and 0.5 and 4 hours postdose The Cmax of IMC-F106C will be reported.
Incidence of anti-IMC-F106C Antibodies Up to ~45 months The incidence of anti-IMC-F106C antibodies, including neutralizing antibodies, will be reported.
Association between PFS and Intra-Tumor Immune Cells Up to ~45 months 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.
Health-Related Quality of Life Up to ~45 months The change from baseline over time and between treatments of health-related quality of life will be reported.
Overall Response Rate (ORR) Up to ~45 months ORR as assessed by BICR according to RECIST 1.1.
Number of Participants Experiencing ≥1 Adverse Event (AE) Up to ~57 months 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.
Number of Participants Experiencing ≥1 Serious Adverse Event (SAE) Up to ~57 months 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.
Number of Participants Experiencing a Dose Interruption, Reduction, or Discontinuation Up to ~45 months The number of participants with a dose interruption, reduction, or discontinuation due to AE will be reported.
Overall Survival (OS) Up to ~57 months OS is the time from randomization to time of death from any cause.
Trial Locations
- Locations (173)
University of Arizona
🇺🇸Tucson, Arizona, United States
University of California - San Diego
🇺🇸La Jolla, California, United States
The Angeles Clinic and Research Institute- West Los Angeles
🇺🇸Los Angeles, California, United States
ESC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
UCLA Hematology/Oncology
🇺🇸Los Angeles, California, United States
Stanford Cancer Institute - Stanford Cancer Center Palo Alto
🇺🇸Palo Alto, California, United States
Saint John's Health Center - John Wayne Cancer Institute (JWCI)
🇺🇸Santa Monica, California, United States
University of Colorado, Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
UConn Health-Farmington (University of Connecticut Health Center (UCHC))
🇺🇸Farmington, Connecticut, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
Scroll for more (163 remaining)University of Arizona🇺🇸Tucson, Arizona, United StatesTerri KatzContact520-621-2029tkatz@arizona.edu