China-based BeiGene (NASDAQ: BGNE, HKG: 6160, SHA: 688235) and SpringWorks Therapeutics Inc., (NASDAQ: SWTX) have published the latest data from a Phase Ib clinical study assessing the combination of BeiGene’s RAF dimer inhibitor lifirafenib and SpringWorks’ MEK inhibitor mirdametinib in advanced or refractory solid tumors carrying RAS mutations, RAF mutations, and other MAPK pathway abnormalities.
Study Design and Patient Treatment
As of January 20, 2023, 71 patients received a total of 9 dose levels of treatment to evaluate different dosing regimens. The results indicate that the combination of lifirafenib and mirdametinib exhibits anti-tumor activity in several types of solid tumors, including low-grade serous ovarian cancer, non-small cell lung cancer, and endometrial cancer, which carry multiple KRAS, NRAS, and BRAF mutations, with a good safety profile. Among 62 evaluable patients, 14 (23%) achieved confirmed objective remission.
Detailed Results and Mutation-Specific Responses
Among the 17 LGSOC patients receiving treatment, 10 patients (59%) achieved objective remission, with a median treatment duration of approximately 26 months. In the 4 endometrial cancer patients receiving treatment, 2 (50%) achieved an objective response to tumors carrying BRAF fusion mutations or KRAS mutations, respectively. Among the 11 NSCLC patients receiving treatment, 2 (18%) achieved objective response to tumors carrying NRAS mutations or BRAF V600E mutations, respectively. The incidence of adverse events during treatment leading to dose-limiting toxicity and termination of administration was relatively low.
Lifirafenib and Mirdametinib’s Individual Profiles
Lifirafenib (BGB-283) has demonstrated anti-tumor activity in cancer patients with V600E type BRAF mutations and non-V600E type BRAF mutations (RAF monomer mutations), and cancer patients with KRAS/NRAS mutations (RAF dimer mutations) in pre-clinical models. Mirdametinib, meanwhile, has obtained orphan drug designation (ODD) status for use in NF1 in the US and Europe, alongside fast-track status in the US for the treatment of neurofibromatosis-associated plexiform neurofibroma (NF1-PN) of ≥ 2 years old with advanced or severe symptoms.-Fineline Info & Tech
