Verastem Oncology announced positive interim data from Part A of the ongoing RAMP 201 (ENGOTov60/GOG3052) international registration-directed Phase 2 study evaluating the safety and efficacy of avutometinib (VS-6766) alone and in combination with defactinib among patients with recurrent low-grade serous ovarian cancer (LGSOC). The Company is also providing a regulatory update following a productive meeting with the U.S. Food and Drug Administration (FDA). Results of RAMP 201 Part A Interim Analysis: The objective of Part A (selection phase) of the RAMP 201 LGSOC study was to select the go forward regimen between avutometinib monotherapy or the combination of avutometinib and defactinib to be studied in Part B (expansion phase) of the study.

In addition, the efficacy was assessed in both KRAS mutant and KRAS wild type LGSOC. Part A randomized eligible patients to avutometinib monotherapy (n=33) or the combination of avutometinib and defactinib (n=31). The combination of avutometinib and defactinib has been declared the go forward treatment regimen based on a higher rate of confirmed objective responses in a planned interim analysis with prespecified criteria.

Overall, patients on the combination arm were heavily pretreated with an average of 4 prior systemic regimens (up to 11), including prior platinum-based chemotherapy, endocrine therapy and bevacizumab in most patients and prior MEK inhibitor therapy in about 20% of patients. Of the 29 patients evaluable for response by blinded independent central review (BICR) in the combination arm, the initial results showed a confirmed objective response rate (ORR) of 28% in all patients and 27% vs 29% in KRAS mutant (n=15) and KRAS wild-type (n=14) LGSOC, respectively. Three additional patients with KRAS mutant LGSOC showed an unconfirmed partial response.

In addition, the vast majority of patients showed tumor regression, as the overall disease control rate (stable disease plus partial response) was 93%. Most evaluable patients (62%) were still on study treatment on the combination arm at the time of the data cut with a minimum follow-up of 5 months. The confirmed ORR for the monotherapy arm by BICR was 7% in evaluable patients (n=30).

The overall disease control rate for the monotherapy arm by BICR was 90%. Across both the combination and monotherapy arms, there have been no additional safety signals reported with a continued favorable safety and tolerability profile. The most common treatment-related adverse events for the combination in all treated patients were diarrhea, nausea, blood creatine phosphokinase (CPK) increased, vision blurred, dermatitis acneiform and rash, fatigue and peripheral edema, most of which were mild to moderate, with 9% discontinuation due to adverse events.

Target enrollment for the combination arm in RAMP 201 has been achieved. The Company is planning a RAMP 201 presentation at a scientific conference in mid-2023. Regulatory Update Following Type B FDA Meeting on LGSOC Program: A recent FDA meeting was held to discuss the encouraging results to date of the ongoing RAMP 201 trial evaluating avutometinib ± defactinib among patients with recurrent LGSOC, confirm the go forward treatment regimen selection and discuss the regulatory path forward.

The combination of avutometinib with defactinib has been selected vs monotherapy as the go forward treatment in all recurrent LGSOC regardless of KRAS status, acknowledging the demonstrated contribution of defactinib. The Company intends to include mature data from RAMP 201, the Verastem sponsored clinical trial, and the FRAME study, led by The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust to potentially support filing for accelerated approval. Both studies are evaluating avutometinib and defactinib in patients with recurrent LGSOC.

The Company is in ongoing discussions with the FDA on the confirmatory study and plans to provide an update after agreement with the FDA. Continued enrollment in the combination arm of RAMP 201 is planned to expand the clinical experience in anticipation of initiation of a confirmatory study.