On June 18, the first patient was randomized into the PRISM-MEL-301 trial (ClinicalTrials.gov identifier NCT06112314), which is assessing the efficacy and safety of brenetafusp (also known as IMC-F106C; PRAME-A02) in combination with nivolumab in the first-line setting of advanced or metastatic cutaneous melanoma, according to the study’s sponsor, Immunocore.
Brenetafusp is the first PRAME (preferentially expressed antigen in melanoma) x CD3 ImmTAC (immune-mobilizing monoclonal T-cell receptor against cancer) bispecific protein targeting an HLA-A*02:01 PRAME antigen.
The PRISM-MEL-301 trial will randomly assign HLA-A*02:01–positive patients with advanced or metastatic cutaneous melanoma to receive brenetafusp plus nivolumab vs a control arm of either nivolumab or nivolumab plus relatlimab, depending on the country, in the first-line setting.
“We are very proud to have started the registrational program for brenetafusp, our PRAME [antigen–targeting] candidate, supported by the recent promising brenetafusp monotherapy data in late-line cutaneous melanoma,” said Mohammed Dar, MD, Senior Vice President of Clinical Development and Chief Medical Officer at Immunocore. “The PRISM-MEL-301 trial—the first phase III trial for any PRAME-targeted therapy—will test whether combining brenetafusp with nivolumab may be a more effective treatment option than current standards of care for newly diagnosed [patients with] metastatic or advanced cutaneous melanoma.”
Phase I data on brentafusp was reported during an oral presentation at the 2024 ASCO Annual Meeting (Abstract 9507). The data showed that brenetafusp was well tolerated as monotherapy and in combination with anti–PD-1 therapy; the results demonstrated clinical activity as monotherapy, including disease control (partial response and stable disease), progression-free survival, and circulating tumor DNA molecular response.
Georgina V. Long, MD, PhD, Co-Medical Director of Melanoma Institute Australia, said: “The PRISM-MEL-301 phase III trial is a great example of outside-the-box scientific thinking, leveraging the immune system in a new way in the hope of beating cancer. My hope is we can get closer to our goal of zero deaths from melanoma by conducting clinical trials with innovative drug therapies such as this.”
Immunocore is continuing to enroll patients into a phase I/II trial in monotherapy and combination arms across multiple tumor types, including three expansion arms for patients with advanced ovarian, non–small cell lung, and endometrial cancers.
