BeiGene, Ltd. (NASDAQ:BGNE, HKEX: 06160))), a commercial-stage biotechnology company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, and SpringWorks Therapeutics, Inc. (NASDAQ:SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, today 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 today in a poster at the American Association for Cancer Research (AACR) 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.
“We have been pleased with the progress of the lifirafenib and mirdametinib combination therapy trial to date, and we look forward to commencing dose expansion cohorts in the coming months,” said Ben Solomon, M.B.B.S., Ph.D., Senior Faculty Member and Medical Oncologist in the Lung and Head & Neck Service at the Peter MacCallum Cancer Centre, who is the principal investigator of the study. “There remains a significant unmet need for the nearly one-third of solid tumor patients whose cancers are driven by RAS mutations, RAF mutations, and other MAPK pathway aberrations, and this combination therapy represents a novel targeted approach for these tumors.”
More information about the ongoing trial of lifirafenib and mirdametinib may be found by searching clinical trial identifier NCT03905148 at https://clinicaltrials.gov.
Details for the AACR 2020 Virtual Meeting II presentation are as follows:
Title: RAF dimer inhibitor lifirafenib enhances the antitumor activity of MEK inhibitor mirdametinib in RAS mutant tumors
Authors: Xi Yuan, Xinwen Zhang, Rong Du, Shing-Hu Cheung, Xikun Wu, Beibei Jiang, Zhiyu Tang, Min Wei, Changyou Zhou, Lai Wang, Todd Shearer, Badreddin Edris, L. Mary Smith, Claire N. Thant, Zhan Yao, Neal Rosen, Lusong Luo
Poster #: 6415
Session: Novel Therapeutic Approaches
Date and Time: June 22, 2020; 9:00 a.m. ET