MapKure, SpringWorks, BeiGene present data from Phase 1a/1b study of BGB-3245

MapKure, SpringWorks Therapeutics (SWTX), and BeiGene (BGNE) presented updated clinical data from the Phase 1a/1b study of BGB-3245, an investigational, selective RAF dimer inhibitor, in adult patients with advanced or refractory solid tumors harboring MAPK pathway aberrations. The ongoing Phase 1a/1b trial is an open-label, dose escalation and expansion study of BGB-3245 in adult patients with advanced or refractory solid tumors harboring MAPK pathway alterations. This portion of the study was designed to evaluate the safety, pharmacokinetics, preliminary antitumor activity of BGB-3245, and to determine its maximum tolerated dose and/or recommended Phase 2 dose to be used in select expansion cohorts. As of the data cut-off of September 1, 2022, 42 patients were treated across six dose levels. Patients were heavily pre-treated, having received a median three prior lines of therapy, including standard of care immunotherapy and targeted therapy regimens. Results demonstrated that BGB-3245 had a manageable safety profile, with adverse event findings consistent with other MAPK pathway inhibitors. The 40 mg once daily dose was determined to be the maximum tolerated dose of BGB-3245. In addition, encouraging anti-tumor activity was observed in heavily pretreated patients, with an objective response rate of 18%. The disease control rate was 79% and clinical benefit rate was 42%. Objective responders include patients with tumors harboring BRAF V600E that had progressed on prior BRAF/MEK inhibitors with or without checkpoint inhibitor treatment, BRAF Class II mutation, BRAF fusion, NRAS and KRAS mutations. Median time on treatment was approximately 5 months and 9 patients remain on treatment. These data supported the advancement of BGB-3245 into the Phase 1b dose expansion portion of the study, which has been enrolling patients since October 2022 in defined cohorts.