Immunocore updates Phase 1 data of brenetafusp (IMC-F106C) in melanoma at ASCO 2024

Immunocore has shared updated Phase 1 results from its clinical trials of brenetafusp (IMC-F106C), an ImmTAC bispecific targeting PRAME, in patients with late-stage cutaneous melanoma who have previously undergone immune checkpoint treatments. These findings were presented at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO). The data demonstrated the potential efficacy and safety of brenetafusp as both a standalone therapy and in combination with anti-PD1 therapies, such as pembrolizumab.

Brenetafusp showed promising results in controlling disease, with partial responses and stable disease observed in a significant number of patients. Of particular interest was the drug's efficacy in patients positive for PRAME, with a 58% disease control rate and a median progression-free survival (PFS) of 4.2 months. The study underscored the association between peripheral blood T cell fitness and improved clinical outcomes, especially in patients who were treated earlier in the course of their disease.

The Phase 1 trial involved 47 patients who received brenetafusp monotherapy at clinically active doses. All participants had previously been treated with immune checkpoint inhibitors, and a high level of PRAME expression was noted in the majority of cases. The tolerability of the treatment was confirmed, with the most common adverse events being low-grade cytokine release syndrome (CRS) and rash, primarily occurring after the initial doses. Notably, there were no instances of Grade 3 or higher CRS events.

Out of the 47 patients, 36 had RECIST evaluable tumors, with a disease control rate of 56%. This included four patients showing partial responses and 16 demonstrating stable disease. Durable tumor reduction was confirmed in 28% of the participants, indicating a sustained response to the treatment. For those with PRAME-positive tumors, the disease control rate was slightly higher at 58%, including all patients with confirmed tumor reduction.

Additionally, molecular responses, as indicated by circulating tumor DNA (ctDNA), were observed in 42% of PRAME-positive patients. This molecular response was linked to longer PFS and overall survival rates. In contrast, no ctDNA reduction was noted in PRAME-negative patients.

Combination therapy with anti-PD1 (pembrolizumab) was also assessed in a smaller cohort of nine patients, all of whom had prior immune checkpoint treatments. Despite being more heavily pre-treated, the combination therapy was well tolerated and showed manageable adverse events consistent with the mechanisms of both drugs. In this group, four out of seven efficacy-evaluable patients achieved disease control, including one ongoing partial response confirmed after the data cutoff.

An intriguing finding from the study was the identification of a gene signature from baseline peripheral blood, which correlated with systemic T cell fitness. Patients with higher levels of this gene expression had better clinical outcomes, including longer median PFS and higher disease control rates.

Currently, Immunocore is progressing with the Phase 3 PRISM-MEL-301 trial, which is enrolling patients with first-line advanced cutaneous melanoma. This trial aims to compare brenetafusp combined with nivolumab against standard treatments. The primary endpoint is progression-free survival, with secondary endpoints including overall survival and response rates.

The Phase 1/2 trial, IMC-F106C-101, continues to explore brenetafusp's efficacy and safety in various solid tumors, with ongoing expansion into multiple cancer types. This adaptive trial structure allows flexibility in assessing the drug's potential across different malignancies.

Cutaneous melanoma remains a significant health challenge, and while recent advancements have been made, there is an ongoing need for new therapies to improve patient outcomes, particularly in those who do not respond to initial treatments. Brenetafusp represents a promising step forward in addressing this need, especially given its novel mechanism of action and potential to enhance immune responses against cancer cells.

Overall, the data presented by Immunocore highlight the continued progress in developing innovative treatments for challenging cancers, with brenetafusp showing potential as an effective therapy for patients with advanced cutaneous melanoma.