FDA Approves First Treatment for KRAS-Mutated Recurrent LGSOC

Author(s):

Key Takeaways

The combination of avutometinib and defactinib is the first FDA-approved treatment for KRAS-mutated recurrent LGSOC.
Approval was based on the phase 2 RAMP-201 trial, showing a 44% overall response rate and a median treatment duration of 12 months.
Serious toxicities were reported by 32% of patients, with 84% experiencing dose interruptions and 44% requiring dose reductions.
The treatment is expected to become available to US patients within a week, with a specific dosing schedule recommended.

FDA approves the first treatment for KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC), offering new hope for patients with this condition.

The FDA Thursday granted accelerated approval to the combination of avutometinib and defactinib (Avmapki Fakzynja Co-pack; Verastem Oncology) for adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who received prior systemic therapy.¹

This accelerated approval, granted well ahead of the June 30 Prescription Drug User Fee Act action date, is based on the phase 2 RAMP-201 trial (NCT04625270) and establishes the combination of avutometinib and defactinib as the first FDA-approved treatment specifically for KRAS-mutated recurrent LGSOC.²

“With this approval, we thank all of the patients and researchers who participated in this trial, and the low-grade serous ovarian cancer community for their contributions to help bring the first FDA-approved treatment for KRAS-mutated recurrent LSGOC and changing the treatment possibilities for RAS/MAPK-pathway-driven cancers," Susana Banerjee, MBBS, MA, PhD, FRCP, global lead principal investigator of ENGOTov60/GOG3052 /NCRI/RAMP201, said in a press release. "We now need to build on this milestone to bring this new treatment to patients around the world.”

The treatment is expected to become available to US adult patients with KRAS-mutated recurrent LGSOC in 1 week.¹ The recommended dosing is 3.2 mg of avutometinib twice weekly (days 1 and 4) and 200 mg of defactinib twice daily, each for 3 weeks of a 4-week cycle until disease progression or intolerable toxicity.

FDA approval graphic | Image Credit: wladimir1804 - stock.adobe.com

FDA approves the first treatment for KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC), offering new hope for patients with this condition. | Image Credit: wladimir1804 - stock.adobe.com

The RAMP-201 trial (NCT04625270) is an open-label multicenter trial that included 57 adult patients with measurable KRAS-mutated recurrent LGSOC who received at least 1 prior systemic therapy, including platinum chemotherapy. They received oral avutometinib and defactinib according to the recommended dosing schedule.

The primary end point was overall response rate (ORR), while the secondary end point was duration of response (DOR). The median duration of treatment was 12 months (range, 0.03-40), with a confirmed ORR of 44% (95% CI, 31-58); the DOR range was 3.3 to 31.1 months.

Of the study population, 32% reported experiencing serious toxicities. Additionally, dose interruptions and reductions due to an adverse effect were experienced by 84% and 44% of patients, respectively. The patients reported various adverse reactions, with the most common including nausea, fatigue, rash, and diarrhea.

“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, global lead principal investigator of GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301, said in a press release.² "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.”

References