In a phase II study (ENGOT-OV60/GOG-3052/RAMP 201) reported in the Journal of Clinical Oncology, Banerjee et al evaluated the efficacy and safety of the RAF/MEK clamp avutometinib in combination with the FAK inhibitor defactinib in patients with recurrent low-grade serous ovarian cancer.
Study Details
In the open-label trial, patients from sites in North America and Europe with measurable disease after ≥ 1 line of platinum chemotherapy were randomly assigned to receive avutometinib monotherapy at 4.0 mg twice weekly or the combination of avutometinib at 3.2 mg twice weekly plus defactinib at 200 mg twice daily. The combination regimen was selected as the go-forward regimen for expansion; findings here are provided only for the combination regimen.
Key Findings
A total of 109 evaluable patients received the go-forward avutometinib plus defactinib regimen. Patients had a median of 3 (range = 1–9) prior lines of therapy. Confirmed objective response on blinded independent central review was observed in 34 patients (31%, 95% confidence interval [CI] = 23%–41%), including complete response in 2 patients. Median duration of response was 31.1 months (95% CI = 14.8–31.1 months). An additional 57% of patients had stable disease. Among 57 patients with KRAS mutation and 52 with wild-type KRAS, objective response rates were 44% and 17%, respectively.
Among all patients in the avutometinib plus defactinib group, median progression-free survival was 12.9 months (95% CI = 10.9–20.2 months), including 22.0 months (95% CI = 11.1–36.6 months) in the KRAS-mutant cohort and 12.8 months (95% CI = 7.4–18.4 months) in the wild-type KRAS cohort.
Among 115 patients in the avutometinib plus defactinib safety population, the most common treatment-related adverse events of any grade were nausea (67%), diarrhea (58%), and peripheral edema (53%). The most common grade ≥ 3 treatment-related adverse events were elevated creatine phosphokinase (24%), diarrhea (8%), and anemia (5%). Adverse events led to treatment discontinuation in 10% of patients.
The investigators concluded: “The efficacy and safety profile of avutometinib in combination with defactinib support this combination as a potential standard of care for recurrent [low-grade serous ovarian cancer]. A randomized phase 3 study of avutometinib and defactinib versus investigator’s choice of therapy for women with recurrent [low-grade serous ovarian cancer] is currently enrolling (RAMP301; ClinicalTrials.gov identifier: NCT06072781).”
Susana N. Banerjee, PhD, MBBS, MA, FRCP, of The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, GTG-UK, London, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Verastem Oncology. For full disclosures of all study authors, visit ascopubs.org.
