Verastem Oncology Seeks FDA Approval for Avutometinib and Defactinib Combination in Low-Grade Serous Ovarian Cancer
核心洞察
Verastem Oncology has completed its NDA submission to the FDA for avutometinib and defactinib to treat low-grade serous ovarian cancer (搜索) (LGSOC (搜索)).
The NDA is based on Phase II RAMP 201 study results, showing a 44% overall response rate and 22-month median progression-free survival in KRAS (搜索) mutant LGSOC (搜索).
The FDA has granted breakthrough therapy and orphan drug designations to the combination therapy for recurrent LGSOC (搜索), potentially expediting its approval.
Verastem Oncology has finalized its New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) for a combination therapy of avutometinib and defactinib, targeting low-grade serous ovarian cancer (搜索) (LGSOC (搜索)). This submission follows the FDA's accelerated approval pathway, with Verastem requesting a priority review, potentially leading to a decision within six months after the 60-day filing period.
The NDA is supported by preliminary data from the Phase II RAMP 201 study, a multicenter, adaptive, randomized, open-label trial. The study evaluated the efficacy and safety of avutometinib alone and in combination with defactinib in patients with recurrent LGSOC (搜索). Results from the study indicated a 44% overall response rate and a median progression-free survival of 22 months in patients with Kirsten rat sarcoma viral oncogene homolog (KRAS (搜索)) mutant LGSOC. The treatment was generally well-tolerated, with a 10% discontinuation rate due to adverse events across all patients.
Rationale Behind the Combination Therapy
Avutometinib functions as an oral rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase (RAF/MEK) clamp, while defactinib is an oral selective focal adhesion kinase (FAK) inhibitor. The combination is designed to target key signaling pathways involved in the proliferation and survival of LGSOC (搜索) cells.
Regulatory Designations and Ongoing Trials
The FDA previously granted breakthrough therapy designation to the avutometinib and defactinib combination for treating recurrent LGSOC (搜索) after one or more prior lines of therapy, including platinum-based chemotherapy. Both agents, alone and in combination, have also received orphan drug designation for LGSOC.
Verastem is currently enrolling patients in the international Phase III RAMP 301 trial, which is intended to serve as a confirmatory study for the initial indication. The company anticipates that this trial will also support an expanded indication, irrespective of KRAS (搜索) mutation status.