Erasca, Inc. announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to naporafenib in combination with trametinib (MEKINIST®) for the treatment of adult patients with unresectable or metastatic melanoma who have progressed on, or are intolerant to, an anti-programmed death-1 (ligand 1) (PD-(L)1)-based regimen, and whose tumors contain an NRAS mutation (NRASm). Naporafenib is an orally available, Phase 3-ready pan-RAF inhibitor with a potential first-in-class and best-in-class profile in NRASm melanoma and other RAS/MAPK pathway-altered solid tumors. FTD is designed to help drugs reach patients faster by facilitating the development and expediting the review of drugs with the potential to fill an unmet medical need by treating a serious or life-threatening condition.

Programs that receive FTD benefit from early and frequent interactions with the FDA during the clinical development process and, if relevant criteria are met, the FDA may consider reviewing portions of a marketing application before the sponsor submits the complete application. NRASm melanoma comprises 20-30% of all melanomas and is associated with a worse prognosis compared to other alterations. Effective treatment options are needed for patients following progression on frontline IO with anti-CTLA-4 and/or anti-PD-(L)1 antibodies.

Currently, chemotherapy is the approved post-IO standard of care with a 7% objective response rate (ORR) and 1.5 months mPFS (historical Phase 3 data generated when the drug was administered in the front-line/second-line setting). While not approved in this indication in the United States, the MEK inhibitor binimetinib is used off label and demonstrated a 15% ORR and 2.8 months mPFS (historical Phase 3 data generated when the drug was administered in the front-line/second-line setting). There are currently no approved therapies that target NRAS mutations.

Erasca recently reported that End of Phase 2 meetings with the FDA and European health authorities confirmed the SEACRAFT-2 Phase 3 trial design and provided clarity on the registrational pathway.