NEW YORK – Clinical-stage precision medicine company MapKure and its joint owners BeiGene and SpringWorks Therapeutics said Thursday that they have kicked off a Phase I clinical trial evaluating BGB-3245, an investigational BRAF inhibitor.
The trial will enroll up to 69 patients with solid tumors who harbor BRAF mutations and are likely to respond to a RAF dimer inhibitor. The companies have dosed their first patient in Australia and will soon expand the study to sites in the US.
BGB-3245 is a second-generation oral BRAF inhibitor that was found to be active against the RAF family kinases. It is designed to inhibit both monomeric and dimeric forms of activating BRAF mutations including V600 and non-V600 mutations. BRAF mutations have been implicated with the development of many different cancers. In preclinical studies, BGB-3245 showed activity against tumor cell lines harboring non-V600 BRAF mutations and in BRAF/MAP-ERK Kinase (MEK) inhibitor-resistant tumors.
In the Phase IA study, researchers will determine the maximum tolerated dose and look at the pharmacokinetics of BGB-3245 in participants with MAPK pathway aberrations. Participants are required to have a known mutation in BRAF, KRAS/NRAS, or any other MAPK pathway aberrations.
In Phase IB, there will be an expansion cohort to further evaluate the pharmacokinetics, safety, and tolerability of BGB-3245 and the preliminary antitumor activity of the drug. In this phase, researchers will focus on patients with solid tumors with non-V600 BRAF mutations including RAF fusions, and BRAF V600 mutated melanoma or non-small cell lung cancer that have progressed on a BRAF-inhibitor or a MEK-inhibitor.
"We believe that BGB-3245 could have meaningful, single-agent antitumor activity in BRAF-altered cancers through its ability to address key primary and resistance gene alterations that are currently unaddressed by approved therapies," Neal Rosen, chair of the MapKure Scientific Advisory Board, said in a statement.
The companies have also previously expressed interest in combining BGB-3245 with MEK inhibitors such as PD-0325901, which is being developed by Pfizer spinoff SpringWorks. PD-0325901 was one of the drugs SpringWorks licensed from Pfizer.