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Erasca Begins Phase III Trial of Naporafenib, Mekinist in NRAS-Mutant Melanoma

NEW YORK – Erasca on Tuesday began the Phase III SEACRAFT-2 trial evaluating its pan-RAF inhibitor naporafenib in combination with Novartis' MEK inhibitor Mekinist (trametinib) in patients with NRAS-mutant melanoma.

The randomized trial will compare second-line treatment with naporafenib plus Mekinist against physician's choice of therapy, which may include chemotherapy or monotherapy treatment with Mekinist. The study will include 470 patients with unresectable or metastatic NRAS mutant melanoma who have progressed on or are intolerant to immunotherapy.

In Stage 1 of the trial, investigators will compare naporafenib plus Mekinist against single agent Mekinist, which will then inform the Phase II dose for the combination.

Stage 2 will evaluate the combination against physician's choice of chemotherapy or a single agent MEK inhibitor using the dual primary endpoints of progression-free survival and overall survival. According to Erasca CMO Shannon Morris, this stage is designed for regulatory approval and will also incorporate feedback from the US Food and Drug Administration and European health authorities.

She added in a statement that initial data from the SEACRAFT-2 trial is expected to read out in 2025. In earlier studies of the naporafenib-Mekinist combination, the median overall survival was 13 months and 14.1 months and progression-free survival was 5.1 months and 4.9 months.

In May, Erasca restructured its pipeline and laid off 18 percent of its workforce to refocus its resources on candidates with the highest probability of success. In the restructuring, naporafenib was chosen to continue development along with two in-licensed candidates, ERAS-0015, a pan-RAS molecular glue, and ERAS-4001, a KRAS inhibitor.