FDA Approves Avmapki Fakzynja Co-pack for KRAS Serous Ovarian Cancer

Avmapki Fakzynja receives accelerated FDA approval for previously treated low-grade serous ovarian cancer with KRAS mutations: © stock.adobe.com.

The United States Food and Drug Administration has granted accelerated approval to the Avmapki Fakzynja Co-pack (a combination of avutometinib and defactinib) for patients with KRAS-mutated, recurrent, low-grade serous ovarian cancer who have received prior systemic therapy, according to a news release from the regulatory agency.

The approval was based on the open-label, multicenter RAMP-201 trial, in which, researchers assessed the efficacy of the investigative treatment in 57 adults. The overall response rate was 44%, based on blinded review using standard criteria. The duration of response was 3.3 to 31.1 months.

All participants had measurable disease and had previously received at least one systemic treatment, including a platinum-based therapy. KRAS mutations were confirmed through local tumor testing. As recommended in the approval, patients took 3.2 milligrams of avutometinib by mouth twice weekly and 200 milligrams of defactinib by mouth twice daily during the first three weeks of each four-week treatment cycle, continuing until their cancer progressed or side effects became intolerable. Dosing used during the trial is considered the recommended 

This drug application was previously also given priority review, which may offer faster review due to unmet medical needs, and the combination had been granted breakthrough therapy designation and orphan drug designation.

Safety of the Drug

The most common side effects, occurring in at least 25% of patients, included both symptoms and lab changes such as high levels of creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, blood bilirubin, triglycerides and alkaline phosphatase.

Other common effects were nausea, fatigue, rash, diarrhea, muscle and joint pain, swelling, low hemoglobin, vomiting, low lymphocyte or neutrophil counts, abdominal pain, indigestion, acne-like rash, vision problems including vitreoretinal disorders and general visual impairment, mouth sores, itching, low platelet count, constipation, dry skin, shortness of breath, cough and urinary tract infections.

Previous Priority Review and Phase 2 RAMP 201 Trial Results

In a previous news release from Verastem Oncology, it was announced that the FDA granted priority review for the new drug application under the accelerated approval pathway for Avmapki Fakzynja Co-pack for the treatment of LGSOC.

The filing was based on a primary analysis of the phase 2 RAMP 201 clinical trial. The overall response rate (ORR) was 31% (34 of 109 patients) by blinded independent central review in all evaluable patients with measurable disease after about 12 months of follow-up. Among patients with LGSOC, the confirmed ORR was 44% (25 of 57 patients), while the KRAS wild-type group had an ORR of 17% (9 of 52 patients).

The median duration of response was 31.1 months in all evaluable patients and in the KRAS-mutant group, and 9.2 months in the KRAS wild-type group. Median progression-free survival was 12.9 months overall, 22 months in the KRAS-mutant population and 12.8 months in the KRAS wild-type population.

The disease control rate at six or more months was 61% overall, with 70% in the KRAS-mutant population and 50% in the KRAS wild-type population.

Avmapki Fakzynja Co-pack continued to show a favorable safety profile, with a 10% discontinuation rate due to side effects and no new safety signals.

“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.,” Dan Paterson, president and chief executive officer of Verastem Oncology, said in the news release. “With the acceptance of this new drug application, 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.”

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