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BeiGene (BGNE) and SpringWorks Therapeutics (SWTX) announced the presentation of preclinical data and provided a program update on their ongoing Phase 1b/2 study evaluating the combination of BeiGene's investigational RAF dimer inhibitor, lifirafenib, with SpringWorks' investigational MEK inhibitor, mirdametinib, in patients with advanced or refractory solid tumors harboring mutations in the MAPK pathway, including those with RAS mutations. The preclinical data were presented in a poster at the American Association for Cancer Research 2020 Virtual Annual Meeting II by researchers from BeiGene, SpringWorks, and Memorial Sloan Kettering Cancer Center. Among the findings presented, lifirafenib and mirdametinib demonstrated potent and synergistic activity in vitro and in vivo across a panel of RAS-mutated cancer models harboring a variety of mutations using clinically relevant concentrations of the compounds. Furthermore, in KRAS Q61K and KRAS G12C xenograft models, the combination demonstrated synergy as validated by pharmacodynamic pathway inhibition and tumor regressions. These preclinical findings provided further support for the ongoing Phase 1b/2 combination study of lifirafenib and mirdametinib, which is evaluating this "vertical inhibition" strategy for treating patients whose cancers harbor RAS mutations and other MAPK pathway aberrations. Based on the progress of the program and the clinical data observed to date, the companies reiterated their previous guidance to complete the dose escalation portion of the trial by the end of 2020 and to commence dose expansion cohorts in tumor types of interest thereafter, including KRAS-mutated non-small cell lung cancer and KRAS-mutated endometrial cancer. Initial clinical data from the trial is expected to be presented at a medical conference in 2021.

SpringWorks Therapeutics (SWTX) announced that the first patient has been dosed in a Phase 1b clinical trial evaluating SpringWorks Therapeutics' investigational gamma secretase inhibitor, nirogacestat, in combination with GlaxoSmithKline's (GSK) investigational anti-B-cell maturation antigen antibody-drug conjugate, belantamab mafodotin, in patients with relapsed or refractory multiple myeloma. The nirogacestat and belantamab mafodotin combination is being evaluated as a sub-study in GSK's ongoing DREAMM-5 platform trial. The Phase 1b combination trial is being advanced pursuant to a global clinical trial collaboration agreement that SpringWorks and GSK entered into in June 2019. Under the terms of the agreement, GSK is sponsoring and conducting the Phase 1b study to evaluate the safety, tolerability and preliminary efficacy of the combination, and is assuming all development costs associated with the study, other than expenses related to the manufacturing of nirogacestat and certain expenses related to intellectual property rights. SpringWorks and GlaxoSmithKline have formed a joint development committee to help manage and oversee the clinical study.