Trial Will Investigate Drug Duo in Solid Cancers With MAPK Pathway Aberrations

The first patient was treated in a sub-study of the phase 1b/2 FIRELIGHT-1 clinical trial investigating tovorafenib (DAY101) plus pimasertib in adolescents and adults with progressive or refractory solid tumors that harbor MAPK pathway aberrations.

“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,” said Dr. Samuel Blackman, co-founder and chief medical officer of Day One, the pharmaceutical company developing tovorafenib.

The phase 1b portion of the trial — which will be conducted at multiple cancer treatment centers across the United States — will look at the safety of combining weekly tovorafenib with pimasertib in about 25 patients aged 12 years and older. The goal here is to determine the optimal dose. Secondary goals also include duration of response, progression-free survival (the time a patient lives from treatment until their disease gets worse) and time to response will be analyzed.

The phase 2 part of the study will analyze safety and efficacy of the dose that was determined in phase 1b in multiple groups of patients that will be subdivided by their genomic characteristics.

Recruitment for the trial is still ongoing.

Both tovorafenib and pimasertib are oral drugs (meaning that they are taken by mouth) that interact with the MAPK signaling pathway, which is involved in gene expression as well as the growth and survival of cells. When the MAPK pathway has an abnormality, it can lead to the proliferation of cancer cells.

“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,” Blackman said.

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