Phase 3 Confirmatory Study of Avutometinib/Defactinib in LGSOC Finalizes Design

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The design of the confirmatory phase 3 RAMP 301 trial evaluating avutometinib (VS-6766) in combination with defactinib (VS-6063) for the treatment of recurrent low-grade serous ovarian cancer (LGSOC) has been finalized by the FDA and Verastem Oncology.¹

The RAMP 301 study is the follow-up confirmatory trial for full approval of the combination for patients with recurrent LGSOC. Based on mature data from the phase 2 RAMP 201 study (NCT04625270) and the investigator-initiated FRAME trial (NCT03875820), there are plans to file an accelerated FDA approval for the combination.

According to recent results from part A of RAMP 201 study, the combination elicited a confirmed objective response rate (ORR) by blinded independent central review of 45% in 13 of 29 patients in the study (95% CI, 26%-64%) and a tolerable safety profile was observed.²​ Additional findings from the RAMP 201 trial showed the combination to be supported among patients with LGSOC regardless of KRAS status.

“We are pleased to partner with GOG and ENGOT and announce the final study design for RAMP 301, another important milestone in advancing our avutometinib and defactinib program and bringing us closer to addressing the unmet needs of patients living with LGSOC,” said Brian Stuglik, chief executive officer, Verastem Oncology, in the press release.¹ "This trial builds on the encouraging results of Part A of the RAMP 201 trial and our breakthrough therapy designation, after one or more prior lines of therapy, and we are committed to bringing the first FDA-approved therapy for LGSOC to patients as quickly as possible.”

Avutometinib is a first-in-class oral RAF/MEK clamp designed to inhibit MEK and block RAF-mediated phosphorylation of MEK2. In the RAMP 301 study, the agent is being combined with the selective FAK inhibitor defactinib.

In the randomized, global, RAMP 301 study, investigators will evaluate the efficacy and safety of avutometinib and defactinib vs standard of care (SOC) chemotherapy and hormonal therapy in patients with recurrent LGSOC.

Approximately 270 patients will be enrolled and randomized to receive either the combination of avutometinib and defactinib or SOC chemotherapy or hormone therapy with the SOC regimen selected based on the preference of the investigator. SOC chemotherapy consists of pegylated liposomal doxorubicin, paclitaxel, and topotecan, and hormone therapy consists of letrozole and anastrozole.

The primary end point being assessed in the study is progression-free survival (PFS). Secondary end points include overall response rate, duration of response​, disease control rate, safety, tolerability, patient reported outcomes, and overall survival.

Enrollment in the confirmatory trial is expected to begin in the second half of 2023.

References:

1. Verastem Oncology announces design for confirmatory trials of avutometinib and defactinib in recurrent low-grade serous ovarian cancer. News release. Verastem Oncology. July 5, 2023. Accessed July 10, 2023. https://tinyurl.com/5avxmxwa

2. Banerjee SN, Ring KL, Nieuwenhuysen EV, et al. Initial efficacy and safety results from ENGOT-ov60/GOG-3052/RAMP 201: a phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC). J Clin Oncol. 2023;41(suppl 16):5515. doi:10.1200/JCO.2023.41.16_suppl.5515