NEW YORK – Verastem Oncology on Monday announced the launch of a Phase II clinical trial of its investigational MEK and pan-RAF inhibitor, VS-6766, as a treatment for recurrent, low-grade serous ovarian cancer patients, including those harboring KRAS mutations.
The registration-enabling study, dubbed GOG3052, will explore the activity of VS-6766 in two parts. In Part A, investigators will randomize patients with KRAS-mutated tumors to receive VS-6766 monotherapy or in combination with Verastem's FAK inhibitor defactinib. Once the optimal strategy is determined based on objective response rates, the trial will proceed to an expansion phase, Part B, in which investigators will assess the efficacy of the chosen regimen in patients who will not be required to harbor KRAS mutations in their tumors.
Verastem is launching the registration enabling study after publishing positive data from a Phase I basket trial, in which VS-6766 was shown to be safe and tolerable. In this earlier study, investigators saw encouraging response rates among patients with both gynecologic and non-small cell lung cancers characterized by RAS-RAF-MEK pathway mutations.
Contingent on the results of the Phase II trial, Verastem plans to seek accelerated approval from the US Food and Drug Administration either for VS-6766 alone or the VS-6766-defactinib combination. The company has not said whether it will seek approval for the biomarker-defined, KRAS-mutated patient population, but the adaptive design of the trial may shed light on this question.
"Results to date have demonstrated the clinical activity of VS-6766 and defactinib in KRAS mutant cancers, signaling potentially promising clinical results in low-grade serous ovarian cancer and in KRAS-G12V mutant non-small cell lung cancer," Verastem CEO Brian Stuglik said in a statement. "The start of our registration-directed trial in recurrent [low-grade serous ovarian cancer] is a significant milestone in our work to develop the backbone of therapy for RAS-driven tumors, an area of minimal therapeutic results, significant toxicity, and limited treatment options."