Boston-based Verastem Oncology (Nasdaq: VSTM) announced receipt of US FDA Fast Track Designation for VS-7375, an oral selective KRAS G12D (ON/OFF) inhibitor, for the treatment of adult patients with KRAS G12D-mutated unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) who have previously received platinum-based chemotherapy and an anti-PD-(L)1 antibody. The designation marks the second Fast Track award for VS-7375, following one granted in July 2025 for KRAS G12D-mutated locally advanced or metastatic pancreatic cancer.
Fast Track Designation enables more frequent FDA interactions, rolling NDA/BLA review, and eligibility for Priority Review and Accelerated Approval, provided the program continues to demonstrate activity in a serious condition with unmet need. The designation also places Verastem among a small group of companies racing to develop the first approved therapy targeting KRAS G12D, one of the most common yet historically undruggable KRAS mutations.
VS-7375 binds both the active (GTP-bound, ON) and inactive (GDP-bound, OFF) conformational states of the KRAS G12D oncoprotein. This differentiates it from inhibitors that target only the OFF state, with the rationale that dual-state engagement may more completely suppress downstream RAS/MAPK signaling and restrict tumor growth. The compound is administered orally once daily.
The NSCLC indication addresses approximately 8,000 patients diagnosed annually in the US with KRAS G12D-mutant disease, representing roughly 5% of NSCLC cases. No FDA-approved therapy currently exists that specifically targets KRAS G12D mutations in any tumor type. Patients with this mutation demonstrate reduced responses to standard systemic regimens and carry a poor prognosis relative to other NSCLC molecular subtypes.
The clinical program supporting the designation centers on TARGET-D 101, a Phase I/II dose escalation, dose expansion, and combination trial initiated in June 2025 in patients with advanced KRAS G12D-mutant solid tumors, including NSCLC, pancreatic, and colorectal cancers. Early clinical data reported in March 2026 showed no dose-limiting toxicities and a generally favorable tolerability profile.