Open-Label Extension Study of Avutometinib Alone or in Combination with Defactinib in Patients with Recurrent Low-Grade Serous Ovarian Cancer

The primary objective is to provide continued treatment with avutometinib alone or in combination with defactinib to participants with recurrent Low‑Grade Serous Ovarian Cancer who are deriving ongoing clinical benefit after completing the RAMP‑201 study, thereby assessing the durability of therapeutic effect in this population. The secondary objective is to monitor and document safety and tolerability of the extended treatment regimen, capturing adverse events and tolerability profiles during prolonged exposure.

The trial enrolled adult female patients with recurrent low‑grade serous ovarian cancer who had completed the RAMP‑201 study and were experiencing continued clinical benefit (complete response, partial response, or stable disease). Participants were required to transition directly into the open‑label extension without a treatment interruption and to have any dose hold of ≤28 days at screening. Selection was based on investigator assessment of ongoing benefit and suitability for continued therapy, with sponsor review for protocol consistency. Female participants of childbearing potential needed to use highly effective contraception and present a negative pregnancy test. All participants provided written informed consent. The sponsor did not provide information on the total number of participants enrolled.

The study is an open‑label extension (OLE) trial evaluating continued administration of avutometinib alone or in combination with defactinib in participants with recurrent low‑grade serous ovarian cancer who completed the preceding RAMP‑201 study and are experiencing ongoing clinical benefit. As a Phase IV, single‑arm, uncontrolled design, the protocol does not incorporate randomization or blinding; all eligible participants receive the oral investigational regimen (400 mg defactinib tablet and 3.2 mg avutometinib hard capsule) on a continuous schedule. Enrollment commenced on 19 May 2026 with an anticipated overall study period ending 29 January 2028. The sequence of study visits includes a screening visit to confirm eligibility, documentation of prior treatment response, contraception status, and a negative pregnancy test; a baseline visit on day 1 of OLE treatment; regular follow‑up assessments (e.g., safety labs, physical examination, and efficacy evaluation) at predefined intervals throughout the treatment period; and a final end‑of‑study visit occurring at study termination or upon early discontinuation. Participant involvement is expected to extend for the duration of continued benefit, up to the planned study end date, with the possibility of earlier withdrawal if the investigator determines loss of clinical benefit, unacceptable toxicity, pregnancy, or non‑compliance with protocol requirements.

The investigational product VS‑6063 contains the active substance defactinib and is formulated as a 400 mg tablet for oral administration. The protocol specifies a dose of 400 mg per administration, taken by mouth.

The investigational product VS‑6766 contains the active substance avutometinib and is formulated as a hard capsule delivering 3.2 mg of the active ingredient for oral administration. The protocol specifies a dose of 3.2 mg per administration, taken by mouth.

Treatment in the study consists of avutometinib administered alone or in combination with defactinib, according to the assigned regimen. No additional non‑experimental comparator, placebo, or standard‑of‑care therapy is provided as part of the study protocol.

Efficacy will be assessed by the investigator’s determination of ongoing clinical benefit, reflecting continued clinical improvement as judged by standard clinical criteria in participants with recurrent Low-Grade Serous Ovarian Cancer. This assessment will be performed throughout the extension period.