55PD - Vemurafenib (VM) in non-melanoma V600 and non-V600 BRAF mutated cancers: first results of the ACSE trial

Date 09 October 2016
Event ESMO 2016 Congress
Session Basic science and translational research
Topics Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Jean-Yves Blay
Citation Annals of Oncology (2016) 27 (6): 15-42. 10.1093/annonc/mdw363
Authors J. Blay1, J. Mazieres2, D. Perol3, F. Barlesi4, D. Moro-Sibilot5, G. Quere6, J. Tredaniel7, X. Troussard8, S. Leboulleux9, D. Malka10, A. Flechon11, C. Linassier12, I.L. Ray-Coquard13, B. Arnulf14, I. Bieche15, G. Ferretti16, F. Nowak17, M. Jimenez18, N. Hoog-Labouret17, A. Buzyn17
  • 1Medical Oncology, Centre Léon Bérard, 69008 - Lyon/FR
  • 2Thoracic Oncology, CHU Toulouse, Hôpital de Larrey, 31059 - Toulouse/FR
  • 3Direction De La Recherche Clinique Et De L'innovation, Centre Léon Bérard, Lyon/FR
  • 4Multidisciplinary Oncology & Therapeutic Innovation, Hopital Nord, 13915 - Marseille/FR
  • 5Thoracic Oncology, CHU Grenoble - Hopital Michallon, 38043 - La Tronche/FR
  • 6Ich, C.H.U. Brest - Hôpital Morvan, Brest/FR
  • 7Service De Pneumologie, Hopital St. Joseph, 75014 - Paris/FR
  • 8Service Of Hematology, CHU de Caen, Caen/FR
  • 9Nuclear Medicine And Endocrine Oncology, Institut de Cancérologie Gustave Roussy, Villejuif/FR
  • 10Digestive Oncology, Institut de Cancérologie Gustave Roussy, 94800 - Villejuif/FR
  • 11Medical Oncology, Centre Léon Bérard, Lyon/FR
  • 12Medical Oncology, CHRU Bretonneau, Tours/FR
  • 13Medecine, Centre Léon Bérard, 69373 - Lyon/FR
  • 14Medical Oncology, Hôpital St. Louis, Paris/FR
  • 15Pharmacogenomic, Institut Curie, Paris/FR
  • 16Radiology, CHU Grenoble - Hopital Michallon, La Tronche/FR
  • 17Research And Innovation, Institut National du Cancer, Boulogne-Billancourt/FR
  • 18R&d, Unicancer, Paris/FR



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
NSCLC 47 31 13 6 7 4 1 43%
Thyroid 3 3 1 2 0%
CK 2 2 1 1 0%
Sarcoma 2 1 1 0%
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%
HCL 4 4 2 2 100%

(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.


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.