Source – Verastem Oncology
The FDA and Verastem Oncology have finalized the design of a Phase III clinical trial to evaluate the efficacy and safety of avutometinib (VS-6766) and defactinib (VS-6063) for the treatment of recurrent low-grade serous ovarian cancer (LGSOC).
The combination of avutometinib and defactinib has shown promising results in previous studies, with a confirmed objective response rate (ORR) of 45% in patients with recurrent LGSOC. The RAMP 301 study will be a randomized, global trial that will enroll approximately 270 patients.
The primary end point of the study is progression-free survival (PFS), and secondary end points include overall response rate, duration of response, disease control rate, safety, tolerability, patient-reported outcomes, and overall survival.
The RAMP 301 study is a follow-up to the Phase II RAMP 201 study, which showed that the combination of avutometinib and defactinib had a confirmed ORR of 45% in patients with recurrent LGSOC. The RAMP 301 study will build on the findings of the RAMP 201 study by evaluating the efficacy and safety of the combination in a larger patient population.
“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. 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.”
– Brian Stuglik, chief executive officer, Verastem Oncology
The combination of avutometinib and defactinib works by targeting two different pathways involved in the growth and spread of cancer cells. Avutometinib is a first-in-class oral RAF/MEK clamp that inhibits MEK and blocks RAF-mediated phosphorylation of MEK2. Defactinib is a selective FAK inhibitor that inhibits the activity of FAK, a protein that promotes cancer cell growth and survival.
The RAMP 301 study is expected to provide further evidence of the efficacy and safety of avutometinib and defactinib for the treatment of recurrent LGSOC. If the study is successful, it could lead to the approval of the combination as a new standard of care for this disease.
Enrollment for the confirmatory trial is anticipated to commence in the latter half of 2023. Around 270 patients will be recruited and assigned randomly to receive one of the following treatments: the combination of avutometinib and defactinib, standard-of-care (SOC) chemotherapy, or hormone therapy, with the specific SOC regimen determined by the investigator’s preference. The SOC chemotherapy regimen consists of pegylated liposomal doxorubicin, paclitaxel, and topotecan, while hormone therapy involves letrozole and anastrozole.
The primary objective of the study is to evaluate progression-free survival (PFS). Secondary endpoints include overall response rate, duration of response, disease control rate, safety, tolerability, patient-reported outcomes, and overall survival.