Binimetinib and encorafenib for the treatment of advanced solid tumors with non-V600E BRAF mutations (mts): Final results of the investigator-initiated phase II BEAVER trial
Abstract
3104 Background: Oncogenic non-V600E BRAF mts are present in many cancer types. Pre-clinical data indicate that some BRAF non-V600E mts can be targeted with BRAF + MEK inhibitors. The BEAVER trial was designed to test the safety and efficacy of binimetinib and encorafenib (B+E) in patients (pts) with non-V600E BRAF mts. Safety data were previously presented [ https://doi.org/10.1016/j.annonc.2021.08.1053 ]. Here, we present the final analysis of the efficacy and exploratory objectives. Methods: Key eligibility criteria were: pts with advanced solid tumors with non-V600E activating (Class 1 and 2) or inhibitory (Class 3) BRAF mts, and no prior BRAF/MEK inhibitors. Pts received binimetinib (45mg PO BID) and encorafenib (450mg PO daily) on a 28-day cycle until intolerable toxicity or progression. The primary objective is OR rate (ORR) as per RECIST 1.1. Secondary objectives included PFS. Log-rank test was used to assess PFS. Exploratory objectives included: development of patient derived xenograft (PDX) models, and genomic/transcriptomic profiling of tumors. Mice bearing PDXs were treated with inhibitors and tumors were measured by caliper measurement. Whole exome and RNAseq was performed on PDXs. Results: From June 2019 to Nov 2023, 27 pts were screened and 23 pts enrolled; 21 are evaluable for ORR. Tumor types were melanoma, colorectal and pancreaticobiliary (n=6 each), lung (n=2), and breast, uterine, and small bowel cancers (n=1 each).Median age was 59 yrs (range 40-73).…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 13 participants or records.
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