OnKure, a leader in discovery and development of next generation histone deacetylase (HDAC) inhibitors, entered into a clinical trial collaboration and supply agreement with Pfizer to support the clinical proof of concept study for MEKTOVI (binimetinib) in combination with OKI-179, a highly potent and tolerable Class I HDAC inhibitor currently in Phase I for the treatment of NRAS melanoma.

Activating NRAS mutations occur in approximately 20% of melanomas, representing the second most common oncogenic driver mutation in melanoma after BRAF mutations. An unmet medical need remains for targeted therapy in metastatic patients harboring an NRAS mutation.

Binimetinib, a mitogen-activated protein kinase (MEK) inhibitor that Pfizer has exclusive rights to in the U.S. and Canada, has been approved for use in combination with encorafenib for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation.

Based on a recent study by Maertens et al. reported in Cancer Discovery, as well as preclinical combination studies conducted by OnKure, the rational combination of these two agents may enhance clinical benefit of MAPK inhibition in NRAS melanomas.

OnKure and Pfizer will form a Joint Development Committee to review clinical trial results from the OnKure-sponsored study.

“We are excited to collaborate with Pfizer on this promising initiative to address unmet need in NRAS melanoma,” said Tony Piscopio, Ph.D., Co-founder, President and Chief Executive Officer of OnKure. “We believe, based on the exceptional tolerability profile of OKI-179, this agent has the potential to provide clinically-meaningful impact and confer a broad therapeutic index in combination with targeted therapeutics across additional tumor types, including CREBP mutant SCLC, ER-positive breast cancer and BRAF melanoma.”

“Recent translational work with my collaborators at Harvard suggests that adding an HDAC inhibitor can further augment binimetinib activity in patients suffering from NRAS melanoma,” said Keith T. Flaherty, M.D., Director of Clinical Research at the Massachusetts General Hospital Cancer Center. “I look forward to this novel combination being tested in patients.”