Abstract
BackgroundThere are no approved treatments specifically for low grade serous ovarian cancer; current standard of care treatment options are limited in efficacy and tolerability. The combination of avutometinib with defactinib has demonstrated efficacy and a consistent safety profile in two clinical trials in recurrent low grade serous ovarian cancer, and a lower discontinuation rate due to adverse events compared with historical rates for standard of care.Primary ObjectiveTo compare the progression free survival of the combination of avutometinib with defactinib versus investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer.Study HypothesisCombination treatment with avutometinib–defactinib will significantly improve progression free survival compared with investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer.Trial DesignGOG-3097/ENGOT-ov81/GTG-UK/RAMP 301 is a phase 3, randomized, international, open label study designed to compare avutometinib with defactinib versus investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer who have progressed on a previous platinum based therapy. On confirmation of disease progression using a blinded independent central review, patients on the investigator’s choice of treatment arm may cross over to the avutometinib–defactinib arm.Major Inclusion/Exclusion CriteriaPatients must have recurrent low grade serous ovarian cancer (KRAS mutant or wild-type) and have documented progression (radiographic or clinical) or recurrence of low grade serous ovarian cancer after at least one platinum based chemotherapy regimen. Unlimited additional previous lines of therapy are allowed, including previous MEK/RAF inhibitor. Patients will be excluded if they have co-existing high grade ovarian cancer or had previous treatment with avutometinib, defactinib, or any other FAK inhibitor.Primary EndpointProgression free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded-independent central review.Sample SizeApproximately 270 patients will be randomized in a 1:1 fashion to either the combination avutometinib with defactinib arm (n~135) or the investigator’s choice of treatment arm (n~135).Estimated Dates for Completing Accrual and Presenting ResultsThe estimated primary completion date of RAMP 301 is 2028, and the estimated study completion date is 2031.Trial RegistrationClinicalTrials.gov NCT06072781