FDA Accepts NDA for KRAS+ Ovarian Cancer Treatment

Verastem Oncology  announced that the FDA has accepted for review the New Drug Application (NDA) under the accelerated approval pathway for avutometinib, an oral RAF/MEK clamp, in combination with defactinib, an oral FAK inhibitor, for the treatment of adult patients with recurrent low-grade serous ovarian cancer (LGSOC), who received at least one prior systemic therapy and have a KRAS mutation. The NDA, which was completed in October 2024, has been granted Priority Review with a Prescription Drug User Fee Act (PDUFA) action date of June 30, 2025. In addition, the FDA has stated that it is not currently planning to hold an advisory committee meeting to discuss the application.

“The FDA filing acceptance and Priority Review for the combination of avutometinib and defactinib underscores the critical unmet need among patients diagnosed with this rare and insidious disease. We are excited by today’s news and to potentially bring the first ever FDA-approved treatment specifically for recurrent KRAS mutant LGSOC to patients in the U.S.,” said Dan Paterson, president and chief executive officer of Verastem Oncology. “With the acceptance of this NDA, we’re taking an important step forward in addressing a condition that has long been overlooked, and we look forward to working with the FDA during its review process and preparing for a commercial launch in mid-2025.”

There are currently no FDA-approved treatments specifically for LGSOC, a rare and distinct ovarian cancer that differs from high-grade serous ovarian cancer in both its biology and how it responds to treatment. Priority Review is granted by the FDA for treatments that offer, if approved, significant improvements over available options or that provide a treatment option where no adequate or approved therapy currently exists.

The filing was based on a primary analysis of the Phase II RAMP 201 clinical trial that evaluated the combination of avutometinib and defactinib in patients with recurrent LGSOC. The results were presented in an oral presentation at the International Gynecologic Cancer Society (IGCS) Annual Global Meeting in October 2024 and demonstrated that the combination of avutometinib plus defactinib resulted in a substantial overall response rate confirmed by blinded independent central review, with responses that were typically durable, and that the combination was generally well-tolerated in patients with recurrent KRAS mutant LGSOC. The NDA also includes supportive data from the FRAME Phase 1 trial, the first study conducted with the combination therapy in recurrent LGSOC.The Company is currently enrolling patients with recurrent LGSOC regardless of KRAS mutation status for RAMP 301, an international Phase 3 trial, which will serve as a confirmatory study for the initial indication and has the potential to support an expanded indication regardless of KRAS mutation status.