Advanced Melanoma
Conditions
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.
Interventions
DRUGBrenetafusp
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.
DRUGNivolumab
Concentrate for solution for infusion at a unit dose of 10 mg/mL.
Concentrate for solution for infusion at a unit dose of 16 mg/mL.
Sponsors
Immunocore Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Overall Survival (OS) | Up to ~57 months | OS is the time from randomization to time of death from any cause. |
| 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. |
| 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. |
| Incidence of anti-IMC-F106C Antibodies | Up to ~45 months | The incidence of anti-IMC-F106C antibodies, including neutralizing antibodies, will be reported. |
| 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, Denmark, Finland, France, Germany, Hungary, Italy, Lithuania, Mexico, Norway, Poland, Portugal, Romania, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTImmunocore Medical Information
CONTACTImmunocore Medical Information EU
Outcome results
None listed