The FDA has approved a groundbreaking combination therapy of avutometinib and defactinib for adults suffering from KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC), marking the first approved treatment for this challenging condition.

This approval is particularly significant for patients who have previously undergone systemic therapy for LGSOC, a cancer type known for its insidious nature and high recurrence rates.

The approval is based on promising results from the phase 2 RAMP-201 trial, which reported a 44% overall response rate and a duration of response ranging from 3.3 to 31.1 months among participants.

This combination therapy represents several firsts in cancer treatment, including the initial registration of a FAK inhibitor and a dual RAF-MEK clamp, showcasing advancements in targeted therapies.

Avmapki (avutometinib) functions by inhibiting MEK kinase activity, while FAKZYNJA (defactinib) serves as a FAK inhibitor, together targeting the RAS/MAPK pathway critical for tumor growth and drug resistance.

Dan Paterson, CEO of Verastem Oncology, emphasized that this treatment offers renewed hope to patients in need of effective options for this rare cancer.

Nicole Andrews from the STAAR Low-Grade Serous Ovarian Cancer Foundation highlighted the importance of this milestone for patients and advocates, celebrating the approval as a significant advancement.

This approval reflects the FDA's commitment to expediting the availability of innovative cancer therapies, ensuring that patients have access to new treatment options.

The safety profile of the therapy includes serious side effects such as ocular disorders and skin toxicities, necessitating careful monitoring during treatment.

The Avmapki Fakzynja Co-pack is expected to be available in the U.S. within one week following its regulatory approval process, which began in May 2024.

The ongoing Ramp 301 study will further explore the efficacy of this drug combination in patients with and without genetic mutations, aiming to solidify its role in treatment.

LGSOC primarily affects women, with an estimated 6,000 to 8,000 cases in the U.S., often diagnosed in younger women and characterized by a median survival rate of about ten years.