Immunocore reports updated brenetafusp data

Immunocore released Phase 1 data with the first off-the-shelf ImmTAC targeting PRAME, brenetafusp, in patients with late-line, post-checkpoint cutaneous melanoma. Brenetafusp was shown to be well tolerated, in monotherapy and in combination with anti-PD1, and demonstrated durable clinical benefit. As of March 18, 47 patients have received brenetafusp monotherapy at clinically active target dose levels. All monotherapy treated patients had received prior immune checkpoint inhibitors. PRAME expression was high amongst evaluable patients. Only 11% of patients had PRAME negative tumors, as measured by immunohistochemistry. Brenetafusp was well-tolerated, with treatment-related adverse events, or TRAEs, that were manageable and consistent with the mechanism of action. The most frequent TRAE reported was Grade 1 or 2 cytokine release syndrome, or CRS and rash; these events occurred predominantly following the initial three doses. There were no Grade 3 or higher CRS TRAEs. Of the 47 monotherapy patients, 36 had a RECIST evaluable tumor assessment. The disease control rate, consisting of partial response and stable disease, was 56% including 4 PR and 16 SD. Durable tumor reduction, confirmed by at least one subsequent scan, was observed in 28% of patients and is an attribute of the ImmTAC platform1. Clinical benefit was enriched in the 31 evaluable PRAME positive patients. The DCR in this group was 58% and included all 10 patients with confirmed tumor reduction. Both median progression free survival and 6-month overall survival rates were greater in PRAME positive than in PRAME negative monotherapy patients: 4.2 vs 2.1 months and 95% vs 40%, respectively. 42% of ctDNA-evaluable, PRAME positive monotherapy patients had a molecular response and there was a trend for longer PFS and OS in molecular responders. No ctDNA-evaluable PRAME negative patients had ctDNA reduction. In addition to the monotherapy patients treated with brenetafusp, there were 9 cutaneous melanoma patients who received brenetafusp in combination with an anti-PD1, all of whom had received prior checkpoint inhibitors. Overall, patients were more heavily pre-treated in the combination cohort compared to monotherapy. Brenetafusp in combination with pembrolizumab was well tolerated, with TRAEs that were manageable and consistent with the mechanism of action of both agents. There was one dose-limiting toxicity reported in one patient with prior history of checkpoint inhibitor induced autoimmune hepatitis. Of the seven patients evaluable for efficacy in combination, four achieved disease control including 1 ongoing PR, and 3 of the 4 ctDNA evaluable patients having molecular response. In 41 gene-expression evaluable monotherapy patients, a gene signature was identified from baseline peripheral blood that was a measure of systemic T cell fitness. Patients with gene signature expression levels greater than or equal to the median had higher clinical benefit including a median PFS of 6 months and DCR of 69%, compared to those with less than the median gene expression levels. Patients with only 1-2 prior lines of therapy had higher T cell fitness gene signature, on average, than those with 3 or more prior lines of therapy. The advanced cutaneous melanoma data from the ongoing Phase 1/2 trial of brenetafusp will be presented today at 2:45 PM CT / 3:45 PM ET, in the Melanoma/Skin Cancers oral abstract session at the 2024 American Society of Oncology Annual Meeting.