FDA Approves Novel Treatment for KRAS-Mutated Ovarian Cancer
The US Food and Drug Administration (FDA) has granted accelerated approval of combination avutometinib and defactinib (Avmapki Fakzynja Co-pack, Verastem, Inc.) for the treatment of certain patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC).
Specifically, approval is for adults who received at least one prior systemic therapy, including a platinum-based regimen, according to the FDA approval notice.
“Prior to this approval, there were no FDA-approved treatments specifically for KRAS-mutated recurrent 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,” Verastem said in a press release.
The FDA approval, which followed priority review, was based on the overall response rate of 44% and duration of response of 3.3-31.1 months demonstrated in the open-label, multicenter, phase 2 RAMP-201 trial of 57 patients with measurable KRAS mutated recurrent LGSOC.
Patients in the study received the recommended dose of 3.2 mg of avutometinib given orally twice weekly on days 1 and 4, and 200 mg of defactinib orally given twice daily — both for the first 3 weeks of each 4-week cycle until disease progression or unacceptable toxicity. The avutometinib-defactinib combination was granted breakthrough therapy designation and orphan drug designation.
Adverse reactions occurring in at least 25% of patients were increased creatine phosphokinase, nausea, fatigue, increased aspartate aminotransferase, rash, diarrhea, musculoskeletal pain, edema, decreased hemoglobin, increased alanine aminotransferase, vomiting, increased blood bilirubin, increased triglycerides, decreased lymphocyte count, abdominal pain, dyspepsia, dermatitis acneiform, vitreoretinal disorders, increased alkaline phosphatase, stomatitis, pruritus, visual impairment, decreased platelet count, constipation, dry skin, dyspnea, cough, urinary tract infection, and decreased neutrophil count.
Full prescribing information will be available at Drugs@FDA.
“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,” Rachel Grisham, MD, Memorial Sloan Kettering Cancer Center, New York, stated.
“I look forward to progressing the confirmatory Phase 3 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,” added Grisham, the Global Lead Principal Investigator of GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301.
Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at [email protected] or on X: @SW_MedReporter.
