Abstract 531P
Background
Recurring oncogenic non-V600E BRAF mts can be identified in many cancers. Preclinical data indicate that they can be targeted with BRAF + MEK inhibitors. BEAVER is an investigator-initiated study designed to test the safety and efficacy of binimetinib and encorafenib (B+E) in patients (pts) with non-V600E BRAF mts.
Methods
Key eligibility criteria are: pts with advanced solid tumors with BRAF non-V600E activating (class 1 and 2) or inhibitory (class 3) mts, and no prior BRAF/MEKi. Pts receive binimetinib (45mg PO BID) and encorafenib (450mg PO daily) on a 28-day cycle until intolerable toxicity or progression. The primary objective is objective response rate (ORR) per RECIST 1.1. In this Simon 2-stage trial, ≥1 of 7 pts must have a response before commencing stage 2 (26 pts total). Secondary objectives include: safety, DCR, and PFS.
Results
From Jun 2019 to Apr 2021, 10 pts were enrolled; 10 are evaluable for safety and 9 for efficacy. Tumor types were: melanoma and colon (n=2 each), gallbladder, lung, breast, ampullary, pancreatic and uterine (n=1 each). Median age was 61 yrs (range 40-72). 1 pt had a class 1, 4 pts had class 2, and 5 pts had class 3, non-V600E BRAF mts. Common treatment-related adverse events were mostly Grade ≤ 2, and included: Blurred vision (70%), fatigue (60%) and nausea (50%). Dose reductions were required in 5/10 pts (50%) due to: blurred vision (20%), central serous retinopathy, malaise, increased lipase and nausea (10% each). Eye toxicities were reversible with dose interruption or reduction. Drug-related Grade 3 AEs occurred in 2/10 pts and included: malaise, confusion, fatigue and increased lipase (10% each). ORR was 22% (2/9) with a confirmed PR in a pt with ampullary cancer (BRAF D594G, class 3) who continues on treatment for 5.4+ months, and an unconfirmed PR in a melanoma pt (BRAF G469S, class 2) treated for 6.5 months. One gallbladder cancer pt (BRAF D594N, class 3) had SD, treated for 4.4 months, and 6 pts had PD as best response.
Conclusions
Preliminary data confirmed the safety of B+E and demonstrated evidence of anti-tumor activity in advanced cancer pts with non-V600E BRAF mts. Enrolment in the BEAVER trial is ongoing.
Clinical trial identification
NCT03839342.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Pfizer.
Disclosure
A. Rose: Financial Interests, Personal, Advisory Board, null: Pfizer. P. Bedard: Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Bicara; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Genentech/Roche; Financial Interests, Institutional, Principal Investigator: Lilly; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Nektar Therapeutics; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Principal Investigator: PTC Therapeutics; Financial Interests, Institutional, Principal Investigator: Sanofi; Financial Interests, Institutional, Principal Investigator: SeaGen; Financial Interests, Institutional, Funding: Servier; Financial Interests, Institutional, Principal Investigator: Zymeworks; Non-Financial Interests, Personal, Leadership Role: AACR Project GENIE; Non-Financial Interests, Personal, Advisory Role: Amgen; Non-Financial Interests, Personal, Advisory Role: BMS; Non-Financial Interests, Institutional, Leadership Role: Breast International Group; Non-Financial Interests, Personal, Leadership Role: Canadian Clinical Trials Group; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: Merck; Non-Financial Interests, Personal, Advisory Role: Pfizer; Non-Financial Interests, Personal, Advisory Role: SeaGen. N. Leighl: Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Funding: Pfizer; Financial Interests, Institutional, Research Grant: Array. L.L. Siu: Financial Interests, Personal, Advisory Board: Arvinas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: GeenSeeq; Financial Interests, Personal, Advisory Board: Janpix; Financial Interests, Personal, Advisory Board: Loxo; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Morphosys; Financial Interests, Personal, Advisory Board: Navire; Financial Interests, Personal, Advisory Board: Oncorus; Financial Interests, Personal, Advisory Board: Phizer; Financial Interests, Personal, Advisory Board: Relay Therapeutics; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Rubius; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Symphogen; Financial Interests, Personal, Advisory Board: Tessa; Financial Interests, Personal, Advisory Board: Treadwell Therapeutics; Financial Interests, Personal, Advisory Board: Voronoi; Financial Interests, Personal, Other: Treadwell Therapeutics; Financial Interests, Personal, Stocks/Shares: Agios; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Avid; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Boerhinger-Ingelheim; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: GSK; Financial Interests, Institutional, Principal Investigator: Intensity Therapeutics; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Mirati; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Roche/Genentech; Financial Interests, Institutional, Principal Investigator: Shattucks; Financial Interests, Institutional, Principal Investigator: Symphogen. A. Spreafico: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Oncorus; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Jannssen; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Symphogen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Surface Oncology; Financial Interests, Institutional, Research Grant: Northern Biologics; Financial Interests, Institutional, Research Grant: Jannssen; Financial Interests, Institutional, Research Grant: Johnson & Johnson; Financial Interests, Institutional, Research Grant: Alkermes; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Alkermes; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Treadwell. All other authors have declared no conflicts of interest.