BOSTON–Â Verastem Oncology has announced that results from its Phase 1/2 FRAME study, which tested the combination of avutometinib and defactinib in patients with solid tumors, have been published in Nature Medicine. The study showed encouraging response rates and extended disease control in patients with low-grade serous ovarian cancer (LGSOC), particularly those with KRAS mutations.
The trial, led by The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust in London, tested the safety and effectiveness of the drug combination across multiple cancer types driven by the RAS/MAPK pathway, including LGSOC, non-small cell lung cancer (NSCLC), and colorectal cancer.
Among 26 LGSOC patients evaluated for treatment response, 42.3% saw their tumors shrink, and the median time before disease progression was 20.1 months. In the subset of patients with KRAS-mutant tumors, the response rate rose to 58.3%, with median progression-free survival reaching 30.8 months.
Only one patient out of 27 stopped treatment due to side effects, and overall the combination was found to be well-tolerated. The most common side effects included rash, elevated enzyme levels, and mild liver toxicity.
“These results support the foundation for the recent FDA approval of the combo in KRAS-mutated recurrent LGSOC,” said Verastem CEO Dan Paterson. “We’re continuing to explore its potential in other cancers.”
Professor Udai Banerji, one of the study’s lead investigators, said the findings mark a step forward for cancers with few effective treatment options. “This was the first study to show clinical activity for this combination. The FRAME data helped establish the dosing now used in ongoing confirmatory trials,” he said.
Verastem is currently running the RAMP 301 Phase 3 trial as a follow-up, and is testing the same drug combination in other cancers, including pancreatic cancer.
