BRAF mutations (mut) are observed in several cancer histotypes at low frequency (
ACSE VM is a phase II trial in patients (pts) with advanced cancers with a BRAF mut identified through the INCa molecular genetic platforms failing standard treatment. Pts with various BRAF V600 mutated cancers (e.g., lung, ovarian, bladder, thyroid, prostate cancers, cholangiocarcinoma (CK), sarcoma/GIST, multiple myeloma, chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL)) are included in dedicated cohorts to receive VM 960 mg BID. Pts with non-V600 BRAF mut (exon 11, 15) or other BRAF alteration are also eligible in a specific miscellaneous cohort (misc.). A Bayesian approach allows sequential analyses in each cohort and early stopping using an inefficacy boundary for objective response (OR) rate of 10%. OR is evaluated every 8 weeks using RECIST V1.1 criteria for solid tumors and specific criteria for myeloma, CLL and HCL.
From Oct. 2014 to Apr. 2016, 78 out of 1500+ screened pts were included at 96 centers. Median age was 67 years [18-84], 51% were females. Median duration of treatment was 1.9 months [0.2-11.0]. Most frequent grade ≥3 AEs were skin and gastrointestinal toxicities.
|Best overall response|
|Included N = 78||Analyzed for response (a) N = 56||CR||PR||SD||PD||Death||Missing||ORR|
|Misc.: V600 mutated Non-V600 mutated||6 14||5 10||0 0||3(b) 0||2 0||0 6||0 3||0 1||60% 0%|
(a) Minimum follow-up of 16 weeks. (b) 1 oligodendroglioma, 1 ganglioglioma, 1 histiocytosis.
Nationwide screening for BRAF mut enabled rapid inclusion of BRAF mutated patients in this basket trial. Antitumor activity of VM was important in NSCLC, HCL, and misc. V600 mutated tumors. Non-V600 mutated tumors derived no benefit.
Clinical trial identification
Legal entity responsible for the study
Unicancer, Inca, ARC.
J-Y. Blay: Advisory board: Roche, Novartis, Bayer, MSD, Lilly, Pharmamar, Deciphera. corporate-sponsored research: Roche, Novartis, Bayer, MSD, Lilly, Pharmamar. D. Perol: Advisory Board: Roche. F. Barlesi: Board: Pfizer. D. Moro-Sibilot: Consultant: Pfizer, Novartis, Lilly, Boehringer, Astra Zeneca, Amgen, BMS. X. Troussard: Advisory Board: Roche, Janssen, Gilead. S. Leboulleux: Consulting: Genzyme, Sanofi, Astra Zeneca, Roche, Merck. Travel: Genzyme, Sanofi, Bayer. D. Malka: Honoraria: Roche, Amgen, Bayer, Teva, Celgene, Lilly, Merck, Merck Serono, Sanofi-Aventis. Consulting: Roche, Merck. Travel: Roche, Sanofi-Aventis.
All other authors have declared no conflicts of interest.