FDA Grants Accelerated Approval to Verastem Oncology’s Avmapki Fakzynja Co-Pack for KRAS-Mutated Recurrent Low-Grade Serous Ovarian Cancer

The FDA has granted accelerated approval to Verastem Oncology’s Avmapki Fakzynja Co-Pack (avutometinib capsules and defactinib tablets). The regulatory action marks the first treatment approved for adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy. According to the company, the approval was based on tumor response rate and duration of response from the Phase II RAMP 201 trial, which demonstrated a meaningful overall response rate and a tolerable safety profile in KRAS-mutated patients.1

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“Today’s 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,” said Dan Paterson, president, CEO, Verastem Oncology, in a press release. “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 US.”

The adaptive, multicenter, parallel cohort, randomized, open-label RAMP 201 trial evaluated the safety and efficacy of avutometinib alone and in combination with defactinib in 225 patients. Part A of the study identified the combination as the go-forward regimen based on response rates, with Parts B and C evaluating its safety and efficacy at standard dosing, and Part D assessing a lower dose of avutometinib to inform individualized dose reduction. The primary endpoint was overall response rate (ORR) assessed by blinded independent central review according to RECIST criteria. The secondary endpoint was duration of response (DOR).^1-3

The primary analysis showed a confirmed ORR of 31% in all evaluable patients with measurable recurrent LGSOC. Among patients with KRAS mutations, the confirmed ORR was 44%, with a median DOR of 31.1 months. In contrast, patients with KRAS wild-type disease had a confirmed ORR of 17% and a median DOR of 9.2 months. Median progression-free survival was 12.9 months in the overall population, extending to 22 months in KRAS-mutated patients and 12.8 months in KRAS wild-type. At six months, the disease control rate was 61% overall, 70% in the KRAS-mutated group, and 50% in the KRAS wild-type group.

The Avmapki Fakzynja Co-Pack was generally well tolerated, with a 10% discontinuation rate due to adverse events (AEs). The most common treatment-related AEs included nausea (67.0%; grade ≥3: 2.6%), diarrhea (58.3%; grade ≥3: 7.8%), and increased blood creatine phosphokinase levels (60.0%; grade ≥3: 24.3%).²

According to the American Cancer Society, an estimated 20,890 women in the United States will be diagnosed with ovarian cancer by the end of 2025, with approximately 12,730 deaths expected. Ovarian cancer is considered uncommon, with a lifetime risk of one in 91. The lifetime risk of dying from the disease is approximately one in 143.⁴

“One of the most devastating aspects of my LGSOC diagnosis was learning there are no FDA-approved treatments for this rare cancer,” said Nicole Andrews, chair, STAAR Low-Grade Serous Ovarian Cancer Foundation, in the press release. “While there were some treatment options at the time that I could try, I made it my mission to advocate for research specific to my disease. Today we're celebrating a milestone with the first-ever FDA-approved treatment option specifically for patients with recurrent LGSOC with a KRAS mutation. The low-grade serous ovarian cancer community is hopeful and excited about the potential benefits of this treatment and the progress toward improving the diagnosis, awareness, and research for LGSOC.”

References

1. FDA Approves the AVMAPKI™ FAKZYNJA™ Combination Therapy as the First-Ever Treatment for Adult Patients with KRAS-mutated Recurrent Low-Grade Serous Ovarian Cancer. Verastem. May 8, 2025. Accessed May 9, 2025. https://investor.verastem.com/news-releases/news-release-details/fda-approves-avmapkitm-fakzynjatm-combination-therapy-first-ever

2. 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. Verastem. October 17, 2024. Accessed May 9, 2025. https://investor.verastem.com/news-releases/news-release-details/verastem-oncology-presents-positive-updated-ramp-201-data

3. A Study of Avutometinib (VS-6766) V. Avutometinib (VS-6766) + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer with and Without a KRAS Mutation (RAMP 201). Clinicaltirals.gov. Accessed May 9, 2025. https://clinicaltrials.gov/study/NCT04625270

4. Key Statistics for Ovarian Cancer. American Cancer Society. Accessed May 9, 2025. https://www.cancer.org/cancer/types/ovarian-cancer/about/key-statistics.html