Avutometinib/Defactinib Leads to Positive Response, Survival Data in Ovarian Cancer
The completion of a new drug application for the combination of avutometinib and defactinib in KRAS-mutant ovarian cancer is expected to be finalized with the FDA by the end of the month.
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The combination of avutometinib (previously VS-6766), an oral RAF/MEK clamp, and defactinib, an oral FAK inhibitor, showed positive overall response rate (ORR) and progression-free survival (PFS) data in patients with recurrent low-grade serous ovarian cancer (LGSOC), according to updated findings from the phase 2 RAMP 201 study (NCT04625270).1
With approximately 12 months of follow-up, confirmed ORR by blinded independent central review was 31% (34/109; 95% CI, 23%-41%) in all evaluable patients, and the confirmed ORR in patients with KRAS-mutant disease was 44% (25/57; 95% CI, 31%-58%). In patients with KRAS wild-type LGSOC, the confirmed ORR was 17% (9/52; 95% CI, 8%-30%).
The median duration of response was 31.1 months (95% CI, 14.8-31.1) in all evaluable patients, 31.1 months (14.8-31.1) in patients with KRAS-mutant disease, and 9.2 months (95% CI, 5.5-not evaluable) in the KRAS wild-type population.
The median PFS rates were 12.9 months (95% CI, 10.9-20.2), 22 months (95% CI, 11.1-36.6), and 12.8 months (95% CI, 7.4-18.4) in the overall, KRAS-mutant, and KRAS wild-type populations, respectively.
In the overall population, the disease control rate at 6 or more months was 61%, with rates of 70% and 50% in the KRAS-mutant and KRAS wild-type populations, respectively.
“The notable response rates and low discontinuation rate seen with the combination of avutometinib and defactinib are significant. These updated results confirm the potential of this new combination therapy to change practice and be the new standard for care for recurrent low-grade serous ovarian cancer, which previously had limited effective treatment options,” said Susana Banerjee, MBBS, MA, PhD, FRCP, global lead investigator of the study, consultant medical oncologist at The Royal Marsden NHS Foundation Trust and team leader in women’s cancers at The Institute of Cancer Research, London, in a press release.
There was a 10% discontinuation rate due to adverse events (AEs) with the combination, and no new safety signals were identified in this analysis. The most common treatment-related AEs included nausea (all grade, 67.0%; grade ≥3, 2.6%), diarrhea (58.3%; 7.8%), and increased blood creatine phosphokinase levels (60.0%; 24.3%).
In May 2024, Verastem Oncology began submitting a rolling new drug application (NDA) to the FDA for this combination in patients with KRAS-mutant LGSOC who received at least 1 prior systemic therapy, with a plan to complete the submission by October 2024.2 Verastem Oncology remains on track to complete the NDA submission by the end of this month and plans to seek accelerated approval and priority review from the FDA.1
