Verastem Gets Nod from FDA for Rare Ovarian Cancer Combo Therapy
The oral combination therapy has been shown to provide a significant overall response rate in LGSOC patients with disease progression despite prior systemic treatment.
Late-stage development biopharmaceutical company, Verastem Oncology, has gained regulatory approval of its oral combination therapy — avutometinib capsules; defactinib tablets (AVMAPKI FAKZYNJA CO-PACK). According to a May 8, 2025 company press release, the U.S. FDA approved the combination therapy under accelerated review as a treatment for adults with Kirsten rat sarcoma gene (KRAS)-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy (1).
The regulatory body’s decision was based upon the results of the Phase II RAMP 201 clinical trial, an open-label, multicenter study, evaluating the efficacy of the combination therapy in 57 patients with measurable KRAS-mutated recurrent LGSOC. Trial participants had received at least one prior systemic therapy, including a platinum-based drug, and were treated with the combination therapy for four weeks. The treatment regimen comprised avutometinib (AVMAPKI) 3.2 mg capsules twice a week for the first three weeks of a four-week cycle and defactinib (FAKZYNJA) 200 mg tablets twice daily for the first three weeks of the four-week cycle.
In the study, the combination therapy demonstrated robust overall response rates in patients with KRAS-mutated LGSOC that had progressed despite prior systemic therapy. Additionally, patients treated with the combination therapy achieved a median progression free survival of over one year — 22 months in KRAS-mutated and 12.8 months in KRAS wild-type populations (2).
“Low-grade serous ovarian cancer is a rare and highly recurrent cancer with limited effective treatment options. This first-ever FDA approval in this disease was based on the primary analysis of the Phase II RAMP 201 trial, in which the combination of avutometinib and defactinib resulted in a significant overall response rate for patients with a KRAS mutation while being generally well tolerated,” said Rachel Grisham, M.D., Section Head, Ovarian Cancer at Memorial Sloan Kettering Cancer Center in New York, NY and Global Lead Principal Investigator of GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301, in the press release (1). “The approval of avutometinib plus defactinib brings a much-needed therapeutic option to patients and establishes this combination as the new standard of care for women with recurrent low-grade serous ovarian cancer harboring a KRAS mutation. I look forward to progressing the confirmatory Phase III trial, RAMP 301, where we look to continue to support the ongoing body of research of this combination in women with and without a KRAS mutation.”
“[This] approval of AVMAPKI FAKZYNJA CO-PACK for patients with KRAS-mutated recurrent low-grade serous ovarian cancer represents not only the first-ever FDA-approved treatment specifically for this rare cancer but also a new day for people living with this disease who have been in desperate need of new treatment options,” added Dan Paterson, President and Chief Executive Officer of Verastem Oncology, in the press release (1). “We are very proud to bring two innovative medicines in one combination treatment to the LGSOC community. We thank the researchers, patients, and their families participating in our clinical trials, the patient advocacy community, the FDA, and everyone at Verastem for their dedication and commitment to helping us bring AVMAPKI FAKZYNJA CO-PACK to patients in the U.S.”
References
Verastem Oncology. FDA Approves the AVMAPKI FAKZYNJA Combination Therapy as the First-Ever Treatment for Adult Patients with KRAS-mutated Recurrent Low-Grade Serous Ovarian Cancer. Press Release, May 8, 2025.
Verastem Oncology. Verastem Oncology Presents Positive Updated RAMP 201 Data for Avutometinib and Defactinib Combination in Recurrent Low-Grade Serous Ovarian Cancer at the International Gynecologic Cancer Society (IGCS) 2024 Annual Meeting. Press Release, Oct. 17, 2024.