Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

COLUMBUS 7-Year Update: A Randomised, Open-Label, Phase 3 Trial of Encorafenib (Enco) + Binimetinib (Bini) vs Vemurafenib (Vemu) or Enco in Patients (Pts) With BRAF V600–Mutant Melanoma (#209)

Andrew Haydon 1 , Dirk Schadendorf 2 3 , Reinhard Dummer 4 , Keith T Flaherty 5 , Caroline Robert 6 , Ana Arance 7 , Jan Willem B de Groot 8 , Claus Garbe 9 , Helen J Gogas 10 , Ralf Gutzmer 11 , Ivana Krajsová 12 , Gabriella Liszkay 13 , Carmen Loquai 14 , Mario Mandalà 15 , Naoya Yamazaki 16 , Carolin Guenzel 17 , Anna Polli 18 , Mahgull Thakur 19 , Aleesandra di Pietro 18 , Paolo A Ascierto 20
  1. Alfred Hospital, Melbourne, VIC, Australia
  2. University Hospital Essen, West German Cancer Center and German Cancer Consortium, Essen, Germany
  3. National Center for Tumor Diseases (NCT)-West, Campus Essen, & Research Alliance Ruhr, University Duisburg-Essen, Essen, Germany
  4. University Hospital Zurich, Zurich, Switzerland
  5. Massachusetts General Hospital, Boston, USA
  6. Gustave Roussy and Paris-Saclay University, Villejuif, France
  7. Hospital Clinic of Barcelona and IDIBAPS, Barcelona, Spain
  8. Isala Oncology Center, Zwolle, The Netherlands
  9. University Hospital Tubingen, Tubingen, Germany
  10. National and Kapodistrian University of Athens, Athens, Greece
  11. Hannover Medical School, Hannover and Ruhr-University Bochum, Minden Campus, Germany
  12. University Hospital Prague, Prague, Czech Republic
  13. National Institute of Oncology, Budapest, Hungary
  14. University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
  15. University of Perugia,, Perugia, Italy
  16. National Cancer Center Hospital, Tokyo, Japan
  17. Pfizer, New York City, USA
  18. Pfizer, Milan, Italy
  19. Pfizer, Sandwich, UK
  20. Melanoma Unit, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy

Background: The randomised, 2-part, multicenter, open-label, phase 3 COLUMBUS study demonstrated enco + bini improved PFS and OS rates vs vemu in pts with BRAF V600–mutant metastatic melanoma. Here we report the 7-year analysis of COLUMBUS part 1.

Methods: Pts with advanced or metastatic BRAF V600–mutant melanoma were randomised 1:1:1 to enco 450 mg QD + bini 45 mg BID, vemu 960 mg BID, or enco 300 mg QD. Pts were treatment (tx)-naïve or progressed after 1L immunotherapy, with no prior BRAF/MEKi tx. Randomisation was stratified by cancer stage (IIIB + IIIC + IVM1a + IVM1b vs IVM1c), ECOG PS (0 vs 1), and prior 1L immunotherapy (yes vs no).

Results: 577 pts were randomised to enco + bini (n=192), vemu (n=191), or enco alone (n=194). Updated analyses were conducted after >93 mo of minimum follow-up (cutoff: Jan 13, 2023). 7-year PFS and OS rates (95% CI) were 21.2% (14.7, 28.4) and 27.4% (21.2, 33.9) in the enco + bini arm and 6.4% (2.1, 14.0) and 18.2% (12.8, 24.3) in the vemu arm, respectively. TEAEs (≥30% with enco + bini) were nausea, diarrhea, vomiting, arthralgia, and fatigue. Grade 3/4 TEAEs (≥5% with enco + bini) were: increased γ-glutamyltransferase, blood CPK and ALT; hypertension; and anemia. 16-20% of pts discontinued tx due to AEs. After tx discontinuation, 15% of pts from the enco + bini arm, 42% from the vemu arm, and 28% from the enco alone arm received BRAF/MEKi tx; 42% from the enco + bini arm, 49% from the vemu arm, and 43% from the enco alone arm received checkpoint inhibitors.

Conclusions: After 100mo of follow-up, the 7-year analysis from COLUMBUS part 1 confirms the long-term sustained efficacy and known safety profile of enco + bini in pts with BRAF V600–mutant metastatic melanoma.

Clinicaltrials.gov identification: NCT01909453