Verastem Oncology (Nasdaq: VSTM) is strategically positioned for a transformative year in 2025, with a focus on the potential U.S. commercial launch of avutometinib in combination with defactinib for patients with recurrent KRAS mutant low-grade serous ovarian cancer (LGSOC). The FDA has granted Priority Review to the New Drug Application (NDA) for this combination, with a Prescription Drug User Fee Act (PDUFA) action date set for June 30, 2025.
The NDA is supported by data from the RAMP 201 trial, which demonstrated positive safety and efficacy results, and the FRAME Phase 1 trial. These findings highlight the potential of avutometinib plus defactinib to address a significant unmet need in patients with recurrent LGSOC.
Regulatory and Commercial Preparations
Verastem's NDA for avutometinib plus defactinib is under accelerated approval pathway. The company anticipates a potential U.S. commercial launch in mid-2025, contingent upon FDA approval. To support this launch, Verastem has established collaborations with Oberland Capital and IQVIA to strengthen its financial position and leverage commercialization infrastructure.
Key milestones expected in 2025 include the publication of primary analyses from the FRAME and RAMP 201 trials in the first half of the year, presentation of additional RAMP 201 trial analyses at a medical meeting in Q1 2025, and completion of enrollment for the international Phase 3 confirmatory RAMP 301 clinical trial by the end of 2025.
Expanding Avutometinib Plus Defactinib to Other Solid Tumors
Verastem is also exploring the synergistic potential of avutometinib plus defactinib in other advanced solid tumors. The RAMP 205 Phase 1/2 clinical trial is evaluating the combination in first-line metastatic pancreatic cancer. Initial interim data presented at the ASCO Annual Meeting in June 2024 showed a confirmed overall response rate (ORR) of 83% (5/6) in patients receiving the combination in the dose level 1 cohort.
Updated data from the RAMP 205 trial is expected in Q1 2025, with a recommended Phase 2 Dose (RP2D) for trial expansion to be chosen in the first half of 2025. Additionally, the RAMP 203 Phase 1/2 study is investigating the triplet combination of avutometinib, defactinib, and LUMAKRAS™ (sotorasib) in KRAS G12C mutant advanced non-small cell lung cancer (NSCLC). Preliminary data from this study showed no dose-limiting toxicities in the triplet combination.
Advancing Early-Stage Pipeline with VS-7375
Verastem is advancing its early-stage pipeline, including VS-7375, a potential best-in-class oral KRAS G12D (ON/OFF) inhibitor. In January 2025, Verastem exercised its option to license VS-7375 from GenFleet Therapeutics. Preliminary clinical data from a Phase 1 dose-escalation study in China demonstrated oral bioavailability, no dose-limiting toxicities, and several partial responses in patients with pancreatic and lung cancers.
Verastem plans to file an investigational new drug (IND) application in the U.S. for VS-7375 in Q1 2025 and initiate a Phase 1/2a trial in the U.S. by mid-2025. Preclinical and clinical data from the Phase 1 study of VS-7375 in China is expected to be shared in the first half of 2025.
About Avutometinib and Defactinib
Avutometinib is an oral RAF/MEK clamp that inhibits MEK1/2 kinase activities and induces inactive complexes of MEK with ARAF, BRAF, and CRAF. Defactinib is an oral, selective inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2). The combination is being evaluated in the RAMP program, including the ongoing RAMP 301 Phase 3 trial in recurrent LGSOC.
