Results from phase 1 of the RAMP 201 study shows efficacy in treating patients with recurrent low-grade serous ovarian cancer with avutometinib plus defactinib, regardless of previous treatment.
Avutometinib (VS-6766) with defactinib demonstrated efficacy as a treatment for patients with recurrent low-grade serous ovarian cancer compared with avutometinib monotherapy, according to subgroup data from a phase 2 study (NCT04625270).1 The data, presented during the 2023 Annual Global Meeting of the International Gynecologic Cancer Society, were discussed in a press release from Verastem Oncology, the developer of the agents.
Among patients who received avutometinib plus defactinib, patients who received 1 to 3 lines of therapy (n=11) experienced a 45.5% ORR (95% CI, 17%-77%). Patients with more than 4 lines of therapy (n=18) had a 44.4% ORR (95% CI, 22%-69%).
Prior to study enrollment, 8.7% (n=2) of patients responded to their last metastatic treatment.
“Patients with recurrent LGSOC currently have no medicines approved by the US Food and Drug Administration and limited treatment options for their disease,” lead investigator Rachel Grisham, MD, section head of ovarian cancer and director of Westchester Gynecologic Medical Oncology at Memorial Sloan Kettering Cancer Center, said in the news release. “The results from this analysis are encouraging as the combination of avutometinib and defactinib demonstrates robust efficacy in recurrent LGSOC irrespective of the number of prior therapies, and for most of which, response to previous therapy was poor.”
The international phase 2, adaptive, multicenter, randomized, open-label study is designed to compare the efficacy and safety of avutometinib monotherapy with avutometinib plus defactinib in patients with heavily pretreated recurrent LGSOC. Part A is designed to determine the optimal regimen based on the ORR of the 2 treatments, while part B is based on the results from part A and aimed to determine the efficacy of the optimal regimen. Patients were randomized to receive 4.0 mg of oral avutometinib alone twice weekly for 3 weeks or 3.2 mg of avutometinib with 200 mg of defactinib for 3 weeks.
Initial results from part A of the RAMP 201 study showed that the combination elicited an ORR of 45% (n=13) and tumor shrinkage in 86% (n=25) in patients who were treated with the combination of avutometinib and defactinib. The disease control rate was 93% for the treatment combination as well. These data were presented at the 2023 ASCO Annual Meeting in June.2
The data presented at the IGCS meeting comprised those of a planned subgroup analysis, which was designed to assess confirmed ORR via blinded independent central review per RECIST v1.1 criteria, and safety in prior lines of therapy (LoT; 1-3 LoT, ≥4 LoT). Efficacy in the context of best response to most recent prior therapy in the metastatic/recurrent setting was also evaluated.
Regarding safety, adverse events (AEs) in both arms ranged from mild to moderate. Frequent AEs included increase in blood creatine phosphokinase (CPK), fatigue, diarrhea, dermatitis acneiform, and rash. Safety and tolerability of avutometinib and defactinib were similar in both the earlier- and later-line settings.
Based on the results of the RAMP 201 study, Verastem Oncology plans to file for accelerated approval with the FDA for the combination of avutometinib and defactinib in the recurrent low-grade serous ovarian cancer population. This treatment combination previously received breakthrough therapy designation from the FDA in 2021 based on the results from the phase 1 FRAME trial (NCT03875820).3
Verastem also plans to initiate phase 3 of the trial before the end of 2023, which will compare the efficacy of avutometinib plus defactinib with standard-of-care chemotherapy or hormone therapy.
Disclosures: Dr Grisham is a paid consultant for Verastem Oncology.