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Day One Biopharmaceuticals Begins Combination Portion of Trial in MAPK-Altered Tumors

NEW YORK – Day One Biopharmaceuticals said Monday that it has dosed the first patients in the combination portion of its Phase Ib/II trial in adolescents and adults with recurrent, progressive, or refractory solid tumors with MAPK pathway aberrations.

The Phase Ib combination study will determine an optimal dose of Day One's investigational compounds tovorafenib and pimasertib, as well as duration of response, time to response, and progression-free survival. This portion of the study will include approximately 25 adolescent and adult patients, the firm said.

Tovorafenib is a type II inhibitor of RAF kinase, and pimasertib inhibits MEK-1 and -2. Day One believes that combining a type II RAF inhibitor and a MEK inhibitor could produce synergistic activity against tumors with MAPK pathway alterations.

In November 2021, the South San Francisco, California-based company began the Phase II tovorafenib monotherapy portion of FIRELIGHT-1. That study includes two cohorts, a melanoma cohort and a tissue agnostic cohort, with overall response as its primary endpoint, plus additional endpoints of safety, duration of response, progression-free survival, and time to response.

Day One is also testing tovorafenib in children with recurrent or progressive low-grade gliomas with BRAF alterations in collaboration with the Pacific Pediatric Neuro-Oncology Consortium.

"The MAPK pathway is one of the most commonly dysregulated cancer signaling pathways. A growing body of preclinical data indicates that the combination of a type II RAF inhibitor and a MEK inhibitor may have synergistic activity against tumors bearing a variety of different MAPK pathway alterations," Samuel Blackman, cofounder and chief medical officer of Day One, said in a statement. "Extending our research into the combination setting in adult and adolescent patients is a logical next step as it allows us to build on tovorafenib's monotherapy activity and uncover its full therapeutic potential in tumors with unaddressed MAPK alterations."