Ovarian cancer treatment is at the forefront as Verastem Oncology, a biopharmaceutical company dedicated to developing new cancer therapies, announced the initiation of a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA). This submission seeks accelerated approval for the combination of avutometinib, an RAF/MEK clamp, and defactinib, a selective FAK inhibitor, aimed at treating adult patients with recurrent KRAS mutant (KRAS mt) low-grade serous ovarian cancer (LGSOC) who have received at least one prior systemic therapy. The rolling review process allows Verastem to submit sections of the application as they are completed, rather than waiting for all sections to be ready.
The initial sections of the NDA submission include the nonclinical and quality sections. Verastem reached an agreement with the FDA to base the primary efficacy analysis on the RAMP 201 study, which includes 12 months of follow-up. The proposed indication for the final submission of the clinical module may be expanded if Verastem provides data showing substantial improvement in the KRAS wild-type (KRAS wt) population.
The FDA has agreed to Verastem’s plan to submit the clinical module in the second half of 2024, completing the NDA application. Previously, the FDA granted Breakthrough Therapy Designation (BTD) for the combination treatment for recurrent ovarian cancer and Orphan Drug Designation (ODD) for certain LGSOC indications. Verastem plans to request a priority review for the NDA.
Dan Paterson, President and CEO of Verastem Oncology emphasized the significance of this milestone: “The initiation of our rolling NDA submission for the avutometinib and defactinib combination is an important step towards addressing the significant unmet needs of patients with KRAS mutant low-grade serous ovarian cancer. The data from our ongoing RAMP 201 trial continues to support our belief that this combination could become a new standard of care for these patients if approved.”
RAMP 201 Phase 2 Study Completes Enrollment and Shows Promising Results for Recurrent LGSOC Treatment
RAMP 201 is a Phase 2 registration-directed study evaluating the combination of avutometinib and defactinib in patients with recurrent ovarian cancer. Enrollment for the study is complete, with 115 patients treated at the recommended Phase 2 dose. The NDA submission is expected to be finalized in the second half of 2024, pending mature safety and efficacy data from the RAMP 201 trial. Verastem also plans to discuss the KRAS wt data with the FDA to determine the potential for expanding the treatment’s approval. The company anticipates presenting the mature dataset at a medical meeting in late 2024.
The interim data from the RAMP 201 study has shown robust overall response rates (ORR) and durable responses with low discontinuation rates due to adverse events. This positive data supports the continued development and potential approval of the avutometinib and defactinib combination.
The FDA granted Breakthrough Therapy Designation for the combination of avutometinib and defactinib for treating all patients with recurrent LGSOC after one or more prior lines of therapy. The combination was also granted Orphan Drug Designation in March 2024, highlighting the rarity and severity of ovarian cancer and the need for new treatment options. LGSOC is highly recurrent and less responsive to chemotherapy compared to high-grade serous ovarian cancer (HGSOC), with current treatments showing limited efficacy and high discontinuation rates due to adverse effects.
Verastem Enrolls Patients in RAMP 301 Phase 3 Trial for New Ovarian Cancer Therapy
Verastem is also enrolling patients in RAMP 301, an international confirmatory Phase 3 trial evaluating the combination of avutometinib and defactinib versus standard care chemotherapy or hormonal therapy for recurrent LGSOC. This trial aims to provide further evidence of the combination’s efficacy and safety.
LGSOC is a rare and challenging form of ovarian cancer, affecting approximately 6,000-8,000 women in the U.S. and 80,000 worldwide. It primarily impacts younger women and has a median survival of about ten years. The disease significantly affects patients’ mental and physical health, fertility, and quality of life. There are currently no FDA-approved treatments specifically for ovarian cancer, making this new combination therapy a potentially critical advancement.
Avutometinib, designed to inhibit the RAS/MAPK pathway, and defactinib, a FAK inhibitor, work together to target cancer cells more effectively. The combination aims to provide a more durable anti-tumor response by inhibiting MEK signaling without the compensatory activation seen with other inhibitors. Verastem’s efforts to advance the development of this combination therapy demonstrate a commitment to addressing unmet needs in cancer treatment, providing hope for patients with LGSOC and other RAS/MAPK-driven tumors. The company continues to engage with the FDA and the medical community to bring this promising therapy to patients as quickly as possible.
Resource: Business Wire, May 24, 2024
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