Verastem Oncology files NDA for ovarian cancer therapy

Verastem Oncology has recently completed the submission of a new drug application (NDA) to the US Food and Drug Administration (FDA) for a combined therapy of avutometinib and defactinib intended for treating low-grade serous ovarian cancer (LGSOC). The application was submitted through the FDA’s accelerated approval pathway, with Verastem also seeking priority review status. If granted, a decision on the NDA could be expected within six months following the 60-day filing period.

Avutometinib is an oral drug that acts as a rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase (RAF/MEK) clamp, while defactinib is an oral selective focal adhesion kinase (FAK) inhibitor. The rolling NDA submission, which began in May 2024, was based on preliminary findings from the Phase II RAMP 201 study. This study was a two-part, multicenter, adaptive, parallel cohort, randomized, open-label clinical trial that evaluated the efficacy and safety of avutometinib alone and in combination with defactinib in patients with recurrent LGSOC.

The Phase II RAMP 201 study yielded promising results, with an overall response rate of 44%, a median progression-free survival of 22 months, and a six-month disease control rate of 70% in patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant LGSOC. The treatment regimen was generally well-tolerated, with only a 10% discontinuation rate due to adverse events across all participants. In addition to data from the RAMP 201 study, the NDA submission includes supportive findings from the FRAME Phase I trial.

The combination therapy had previously received breakthrough therapy designation from the US FDA for treating patients with recurrent LGSOC who have undergone one or more previous lines of therapy including platinum-based chemotherapy. Furthermore, avutometinib, both alone and in combination with defactinib, has been granted orphan drug designation status for the treatment of LGSOC.

Verastem is also actively enrolling participants in the international Phase III RAMP 301 trial, which is set to serve as a confirmatory study for the initial indication. This trial is anticipated to support an expanded indication for the combination therapy, regardless of the KRAS mutation status of the patients.