Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Phase III Study of Adjuvant Encorafenib Plus Binimetinib Versus Placebo in Fully Resected Stage IIB/C BRAFV600-Mutated Melanoma: COLUMBUS-AD Study Design (#180)

Victoria Atkinson 1 , Axel Hauschild 2 , Georgina V Long 3 , Mario Mandala 4 , Michal Kicinski 5 , Anne-Sophie Govaerts 6 , Isabelle Klauck 7 , Monia Ouali 7 , Paul C Lorigan 8 , Alexander M M Eggermont 9 , Alexander CJ van Akkooi 10
  1. Princess Alexandra Hospital and Greenslopes Private Hospital, Woolloongabba, QLD, Australia
  2. Department of Dermatology, University Hospital (UKSH),, Kiel, Germany
  3. Melanoma Institute Australia, The University of Sydney, and Mater and Royal North Shore Hospitals, Sydney, Australia
  4. University of Perugia, Ospedale Santa Maria della Misericordia, Perugia, Italy
  5. EORTC Headquarters, Brussels, Belgium
  6. EORTC Headquarters, Brussels, Belgium
  7. Pierre Fabre, France
  8. Christie NHS Foundation Trust, Manchester, United Kingdom
  9. University Medical Center Utrecht, Utrecht, Netherlands
  10. Melanoma Institute Australia, University of Sydney, Royal Prince Alfred Hospital, Sydney, NSW, Australia

Background: COLUMBUS demonstrated the safety and efficacy of encorafenib + binimetinib for BRAFV600E/K-mutant advanced melanoma. Stage IIB/C melanoma has ≥ risk of recurrence and mortality versus stage IIIA/B, for which there are multiple treatments available. Until recently, standard of care for stage II melanoma was surveillance post-resection, and there is currently only one IO approved globally in this setting. Thus, there is need for more treatment options for BRAF-mut stage II disease. Here we report the rationale and design of COLUMBUS-AD (NCT05270044).

Trial Design: COLUMBUS-AD is a worldwide, multicenter, placebo-controlled, randomised, triple-blind Phase 3 study evaluating adjuvant encorafenib + binimetinib treatment versus double matched placebos in patients with fully resected stage IIB/C BRAFV600-mutant melanoma. Approximately 2200 patients will be screened to enroll 815. More than 170 sites in ≤ 26 countries will participate in the study conducted in collaboration with the EORTC. Patients will receive treatment for 12 months, or until disease recurrence. Participants will be followed monthly during treatment, every 3 months for 3 years, then regularly for 10 years. Inclusion criteria include adult patients (³18 years), fully resected stage IIB/C cutaneous melanoma within 12 weeks of negative SLNB staging, no other signs of metastases, fully recovered from surgery, ECOG 0/1, adequate hematologic, hepatic, cardiac, coagulation and renal functions. Molecular screening to confirm BRAFV600E/K-mutant status will be performed by a central laboratory. Eligible patients are randomised 1:1 to receive encorafenib 450 mg once daily + binimetinib 45 mg twice daily or matching placebos. The primary endpoint is RFS. Secondary endpoints include DMFS, OS, QoL, safety and tolerability between the two arms, and PK data. The first patient was screened in May 2022, and accrual is anticipated to be completed by mid-2025.

Conclusion: COLUMBUS-AD is the first phase 3 randomised trial to evaluate adjuvant BRAFi/MEKi in stage IIB/C melanoma.