Verastem Oncology (Nasdaq: VSTM) has announced the completion of its rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) for the combination of avutometinib and defactinib. This therapeutic approach targets adult patients with recurrent KRAS mutant low-grade serous ovarian cancer (LGSOC) who have previously undergone at least one systemic therapy. The company is seeking accelerated approval and priority review, anticipating a decision from the FDA by the end of 2024 and potential approval by mid-2025.
The submission is based on data from the RAMP 201 trial, which demonstrated promising response rates and a favorable safety profile. The company is also preparing for a potential U.S. commercial launch in mid-2025.
RAMP 201 Trial Data
Updated data from the RAMP 201 trial, presented at the International Gynecologic Cancer Society (IGCS) 2024 Annual Meeting, highlighted the efficacy and safety of the avutometinib and defactinib combination. The primary analysis, with a data cutoff of June 30, 2024, showed a confirmed overall response rate (ORR) by blinded independent central review (BICR) of 31% (34/109; 95% CI: 23-41) in the overall population. In the KRAS mutant LGSOC subgroup, the ORR was 44% (25/57; 95% CI: 31-58), while in KRAS wild-type LGSOC, it was 17% (9/52; 95% CI: 8-30). Notably, 82% of all patients experienced a reduction in tumor size, regardless of KRAS status. The combination was generally well-tolerated, with a 10% discontinuation rate due to adverse events and no new safety signals identified.
Financial Position
Verastem Oncology reported its financial results for the third quarter of 2024, ending with $113.2 million in cash, cash equivalents, and short-term investments. This financial runway is expected to sustain the company through mid-2025, potentially covering the period of anticipated FDA approval and initial commercial launch. However, total operating expenses for the quarter increased to $37.0 million, compared to $21.3 million in Q3 2023, driven by higher research and development (R&D) and selling, general, and administrative (SG&A) costs. The net loss for Q3 2024 was $24.0 million, or $0.60 per share, compared to a net loss of $20.0 million, or $0.75 per share, in Q3 2023.
Strategic Pipeline Adjustments
Verastem has decided to discontinue the Phase 1/2 RAMP 204 clinical trial, which was evaluating the combination of avutometinib and adagrasib in patients with KRAS G12C-mutant NSCLC. This decision allows the company to prioritize the Phase 1/2 RAMP 203 clinical trial, assessing the doublet of avutometinib and sotorasib, and the triplet combination of avutometinib, sotorasib, plus defactinib in similar patient populations. Updated interim data from the doublet combination and initial safety data from the triplet combination are expected by the end of 2024.
VS-7375/GFH375: Oral KRAS G12D Inhibitor
GenFleet Therapeutics has initiated a Phase 1/2 trial in China evaluating VS-7375/GFH375, a KRAS G12D inhibitor, in patients with KRAS G12D-mutated advanced solid tumors. Verastem anticipates filing a U.S. investigational new drug (IND) application for VS-7375/GFH375 by Q1 2025.
