Avutometinib and Defactinib Show Promise in Treating Ovarian Cancer

In a significant development for the treatment of recurrent low-grade serous ovarian cancer (LGSOC), the combination therapy of avutometinib and defactinib has demonstrated a favorable safety profile and enhanced efficacy in a recent clinical trial. This phase 2 trial, known as RAMP 201, included 115 patients and was published in the Journal of Clinical Oncology on July 11, 2025. The findings indicate that only five patient deaths occurred, none related to the treatment regimen.

The results revealed that the median progression-free survival (PFS) for patients receiving the combination therapy was 12.9 months, while the objective response rate (ORR) was significantly higher at 31% compared to 17% for those receiving avutometinib alone. Additionally, 29% of patients in the combination arm achieved a partial response, and 2% achieved a complete response.

Dr. John Hayslip, Chief Medical Officer at Verastem Oncology, emphasized the importance of these findings, stating, "The publication of the primary analysis of the RAMP 201 study reflects the meaningful clinical advancement demonstrated by the combination of avutometinib plus defactinib for patients with recurrent low-grade serous ovarian cancer." This study's outcomes have supported the recent FDA approval of the combination therapy for patients with KRAS-mutated recurrent LGSOC.

The trial's design included a randomized assignment of patients aged 18 years and older, with a histologically confirmed diagnosis of LGSOC, to either the combination treatment or to monotherapy with avutometinib. The combination group received oral doses of avutometinib and defactinib, with 81% of responders maintaining their response at six months, and 72% at twelve months. Notably, the median time to confirmed response in the combination arm was 3.7 months.

Safety assessments indicated that treatment-related adverse events were common, with nausea (67%), diarrhea (58%), and peripheral edema (53%) being the most frequently reported. Serious adverse events occurred in 7% of patients, with 10% discontinuing treatment due to adverse effects, primarily elevated creatine phosphokinase levels.

Experts in the field have acknowledged the significance of these findings. Dr. Sarah Johnson, Professor of Oncology at the University of Pennsylvania, commented, "The results from this trial pave the way for further exploration of combination therapies in managing recurrent ovarian cancer, particularly for patients with limited treatment options."

The RAMP 201 trial represents a pivotal step in addressing the urgent need for effective treatments in recurrent low-grade serous ovarian cancer. The promising results will likely influence ongoing research and the design of future clinical trials, including the global phase 3 RAMP 301 trial, which aims to further investigate the efficacy of this combination therapy in broader patient populations. As the oncology community awaits additional findings, these initial results offer hope for improved outcomes in a challenging cancer subtype.

The ongoing exploration of combination therapies, particularly in the context of genetic mutations such as KRAS, highlights the evolving landscape of cancer treatment, where personalized medicine continues to gain traction. The implications of these results extend beyond clinical efficacy; they also raise awareness about the importance of targeted therapies in improving patient quality of life and survival rates. As research progresses, it may lead to a redefined treatment paradigm for low-grade serous ovarian cancer and potentially other malignancies.