Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

BEACON CRC: a randomized, 3-Arm, phase 3 study of encorafenib (ENCO) and cetuximab (CETUX) with or without binimetinib (BINI) vs. choice of either irinotecan or FOLFIRI plus cetuximab in BRAF V600E–mutant metastatic colorectal cancer (#123)

Jayesh Desai 1 , Scott Kopetz 2 , Axel Grothey 3 , Eric Van Cutsem 4 , Rona Yaeger 5 , Harpreet Wasan 6 , Takayuki Yoshino 7 , Fortunato Ciardello 8 , Ashwin Gollerkeri 9 , Kati Maharry 9 , Fotios Loupakis 10 , Yong Sang Hong 11 , Neeltje Steeghs 12 , Tormod Kyrre Guren 13 , Hendrik-Tobias Arkenau 14 , Pilar García Alfonso 15 , Timothy Price 16 , Andrew Strickland 17 , Niall Tebbutt 18 , Christos Karapetis 19 , Lorraine Chantrill 20 , Felicity Murphy 21 , Victor Sandor 22 , Janna Christy-Bittel 9 , Lisa Anderson 9 , Josep Tabernero 23
  1. Peter MacCallum Cancer Centre, Melbourne, Australia
  2. UT MD Anderson Cancer Center, Houston, USA
  3. Mayo Clinic, Rochester, USA
  4. UZ Leuven-Campus Gasthuisberg, Leuven, Belgium
  5. Memorial Sloan-Kettering Cancer Center, New York, USA
  6. Hammersmith Hospital, London, UK
  7. National Cancer Center Hospital East, Kashiwa, Japan
  8. University of Campania, Naples, Italy
  9. Array BioPharma Inc, Boulder, USA
  10. Istituto Oncologico Veneto IOV-IRCCS, Venice, Italy
  11. Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  12. Netherlands Cancer Institute, , Amsterdam, Netherlands
  13. Oslo University Hospital, Oslo, Norway
  14. Sarah Cannon Research Institute and University College London, London, UK
  15. Hospital Gregorio Maranon, Madrid, Spain
  16. Queen Elizabeth Hospital, Adelaide, Australia
  17. Monash Health, Melbourne, Australia
  18. Austin Health, Olivia Newton John Cancer Centre, Melbourne, Australia
  19. Flinders Medical Centre, Adelaide, Australia
  20. St Vincents Hospital, Sydney, Australia
  21. Mater Cancer Care Centre, Brisbane, Australia
  22. Array BioPharma Inc, Cambridge, MA, USA
  23. Vall d’Hebron University Hospital, Barcelona, Spain

BRAF V600E mutations are identified in ≤15% of metastatic colorectal cancer (mCRC) patients and confer a poor prognosis. In patient’s refractory to initial therapy, ORR to standard chemotherapy and biologic combinations are generally <10%, with median PFS and OS of ~2 and 4-6 months, respectively.

The BEACON CRC Study (NCT02928224) was a multicenter, randomized, open-label, 3-arm, phase 3 study evaluating ENCO+CETUX +/- BINI (triplet or doublet combination) vs. investigator’s choice of irinotecan or FOLFIRI + CETUX (control) in patients with BRAF V600E‒mutant mCRC who had failed 1 or 2 prior regimens in the metastatic setting. Primary endpoints were OS and ORR (blinded central review) for the triplet vs. control arm; secondary endpoints included OS for the doublet vs. control arm, as well as PFS, duration of response, and safety.

665 patients were randomly assigned to receive; triplet combination (n = 224), doublet combination (n = 220), or control regimen (n = 221). Median OS was 9.0 months(95% CI, 8.0-11.4) for the triplet vs. 5.4 months(95% CI, 4.8-6.6) for control regimens(HR, 0.52; 95% CI, 0.39-0.70, P < .0001). Confirmed ORR(blinded central review) was 26% (95% CI, 18% to 35%) for the triplet vs. 2% (95% CI, <1% to 7%) for control (P < .0001). Median OS for the doublet was 8.4 months (95% CI, 7.5-11.0) (HR vs. control, 0.60; 95% CI, 0.45-0.79; P = .0003). Adverse events(AEs) were consistent with prior trials with each combination. AEs ≥grade 3 occurred in 58%, 50%, and 61% of patients in the triplet, doublet, and control arms respectively.

ENCO+BINI+CETUX improved OS and ORR in patients with BRAF V600E-mutant mCRC compared with current standard of care chemotherapy and had a safety profile consistent with the known safety profile of each agent. This targeted therapy regimen should be a new standard of care for this patient population.