Verastem Oncology Unveils Bold 2025 Priorities for RAS/MAPK Pathway Cancer Pipeline
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company dedicated to advancing new treatments for RAS/MAPK pathway-driven cancers, has outlined its strategic priorities for 2025, as well as the key milestones it expects to achieve in its novel clinical pipeline. The company’s 2025 goals focus on continuing its progress in the oncology space, with a particular emphasis on expanding the regulatory approval and commercialization of its investigational therapies, such as the combination of avutometinib and defactinib.
“We ended 2024 having made tremendous progress across our pipeline programs, including FDA acceptance of our NDA with Priority Review for avutometinib plus defactinib in recurrent KRAS mutant low-grade serous ovarian cancer,” said Dan Paterson, President and CEO of Verastem Oncology. “As we head into 2025, we are building on the foundational milestones achieved in 2024 and are poised for a transformative year of growth as we evolve into a commercial-stage company while advancing several clinical programs.” With the addition of VS-7375, a novel oral KRAS G12D (ON/OFF) inhibitor, Verastem is well-positioned to strengthen its leadership in treating cancers driven by the RAS/MAPK pathway.
2025 Strategic Priorities for Growth
Verastem’s 2025 strategic priorities center around three main objectives:
- Launch of Avutometinib Plus Defactinib in the U.S. for Recurrent KRAS Mutant Low-Grade Serous Ovarian Cancer (LGSOC): Verastem is focused on advancing its combination therapy of avutometinib and defactinib for patients with recurrent KRAS mutant LGSOC. The company is targeting a successful launch of this combination therapy in the U.S. following its NDA acceptance by the U.S. FDA under the accelerated approval pathway. The FDA has granted Priority Review for this combination therapy, with a Prescription Drug User Fee Act (PDUFA) action date set for June 30, 2025.
- Maximizing the Synergistic Potential of the Combination for Other Advanced Solid Tumors: Verastem is also committed to expanding the clinical evaluation of the avutometinib and defactinib combination in other cancers. By leveraging this combination in multiple solid tumor types, Verastem aims to open new market expansion opportunities, driving further clinical validation and potential approval.
- Advancing Early-Stage Pipeline, Including VS-7375 for KRAS G12D Mutant Cancers: Verastem is progressing with its early-stage pipeline, including VS-7375, an oral KRAS G12D (ON/OFF) inhibitor. This drug has the potential to treat several cancer types, such as metastatic pancreatic cancer, non-small cell lung cancer (NSCLC), and other KRAS G12D mutant solid tumors. The company intends to advance this promising candidate further, with plans for clinical trials set to begin in 2025.
Regulatory Milestones and Approvals
One of the most significant events for Verastem in 2025 will be the expected FDA decision on the approval of the combination of avutometinib and defactinib for recurrent KRAS mutant LGSOC. The positive results from clinical trials such as the RAMP 201 and FRAME trials, which demonstrated encouraging safety and efficacy data, have laid the foundation for this pivotal decision. The company is also advancing regulatory pathways for this combination in Japan and Europe.
Verastem’s strategic partnerships, including those with Oberland Capital and IQVIA, are instrumental in positioning the company for a successful launch. These collaborations have helped strengthen the company’s financial position and prepared it for commercialization in the U.S. while facilitating broader global market expansion.
Key Clinical Trials and Data Updates Expected in 2025
Verastem’s clinical pipeline will see several important updates in 2025, including:
- RAMP 205 Trial: This Phase 1/2 trial is evaluating the combination of avutometinib and defactinib with chemotherapy in patients with metastatic pancreatic cancer. Updated data from this trial is expected to be reported in Q1 2025, with a recommended Phase 2 dose (RP2D) likely to be chosen by mid-2025.
- RAMP 203 Trial: This trial investigates the combination of avutometinib, defactinib, and LUMAKRAS™ (sotorasib) in advanced NSCLC patients with KRAS G12C mutations. Enrollment for this trial is expected to be completed in Q1 2025, with an interim update expected later in the year.
- VS-7375 Development: In addition to progressing with VS-7375 in China, where the drug is undergoing a Phase 1/2 trial, Verastem plans to file an Investigational New Drug (IND) application in the U.S. for VS-7375 by Q1 2025. This will allow the company to initiate a Phase 1/2a trial in the U.S. by mid-2025.
The Science Behind Avutometinib and Defactinib
Avutometinib is a novel oral RAF/MEK clamp that inhibits MEK kinase activity and interferes with the ability of RAF to activate MEK. This mechanism allows the drug to block the RAS/MAPK pathway more completely and durably than existing MEK inhibitors. When combined with defactinib, an inhibitor of focal adhesion kinase (FAK), the therapy targets both tumor cell survival and resistance mechanisms, making it a potent combination for cancers driven by the RAS/MAPK pathway.
