e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

EORTC 1325-MG/KEYNOTE-054 phase 3 trial of pembrolizumab versus placebo for completely resected high-risk stage III melanoma: pembrolizumab crossover and rechallenge following recurrence (#310)

Victoria Atkinson 1 , Alexander M.M. Eggermont 2 , Andrey Meshcheryakov 3 , Christian U. Blank 4 , Mario Mandala 5 , Georgina V. Long 6 , Catherine Barrow 7 , Anna Maria Di Giacomo 8 , Rosalie Fisher 9 , Shahneen Sandhu 10 , Ragini Kudchadkar 11 , Pablo Luis Ortiz Romero 12 , Inge Marie Svane 13 , Alexander van Akkooi 4 , Clemens Krepler 14 , Nageatte Ibrahim 14 , Sandrine Marreaud 15 , Michal Kicinski 15 , Stefan Suciu 15 , Caroline Robert 16
  1. Princess Alexandra Hospital, University of Queensland, Brisbane, Australia
  2. Princess Máxima Center and University MC Utrecht, Utrecht, The Netherlands
  3. Federal State Budgetary Institution “Russian Oncology Scientific Centre named after N.N. Blokhin RAMS” , Moscow, Russian Federation
  4. Netherlands Cancer Institute – Antoni van Leeuwenhoek, Amsterdam, The Netherlands
  5. Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
  6. Melanoma Institute Australia, The University of Sydney, and Mater and Royal North Shore Hospitals, Sydney, Australia
  7. Wellington Hospital, Wellington, New Zealand
  8. Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy
  9. North Shore Hospital - Waitemata DHB, Takapuna, New Zealand
  10. Peter MacCallum Cancer Centre, Melbourne, Australia
  11. Emory University, Atlanta, Georgia, USA
  12. Hospital Universitario 12 De Octubre, Madrid, Spain
  13. Herlev Hospital - University Copenhagen, Herlev, Denmark
  14. Merck & Co., Inc., Kenilworth, New Jersey, USA
  15. EORTC Headquarters, Brussels, Belgium
  16. Gustave Roussy Cancer Campus Grand Paris & University Paris-Saclay, Villejuif, France

Aims: In the phase 3 EORTC 1325-MG/KEYNOTE-054 trial, pembrolizumab improved RFS (HR 0.57) and DMFS (HR 0.60) vs placebo and showed manageable safety in patients with stage III cutaneous melanoma and complete lymph node resection. We present data for patients who recurred and crossed over or were rechallenged with pembrolizumab per protocol. 

Methods: Patients were randomized to pembrolizumab 200mg (N=514) or placebo (N=505) Q3W for 18 doses. Those who recurred without brain metastases and had an ECOG PS 0-2 could enter part 2 and receive pembrolizumab 200mg Q3W ≤2yr for crossover (recurrence after placebo) or rechallenge (recurrence ≥6mo after completing pembrolizumab).

Results: As of 16-Oct-2020, 298 (59%) placebo patients recurred and 155 crossed over. 297 (58%) pembrolizumab patients completed adjuvant pembrolizumab and 20/47 who recurred ≥6mo after completing therapy were rechallenged. Median follow-up for crossover and rechallenge was 41mo and 19mo. Among crossover patients, median part 2 PFS was 8.5mo (95% CI 5.7-15.2) and 3-yr PFS rate was 32%; based on stage at part 2 baseline, median PFS (95% CI) was 14mo (5-27) in stage III-resected patients and 8mo (5-15) in stage IV-unresected, III-C-unresected, or IV-resected patients. ORR in the 80 evaluable stage IV crossover patients was 39% (14 CRs, 17 PRs), 2-yr PFS rate from response was 69% (95% CI 48-83), and from crossover, median PFS was 6.1mo (95% CI 4.1-15.2) and 3-yr PFS rate was 31%. Among rechallenge patients, median part 2 PFS was 4.1mo (95% CI 2.6-NE); for the 9 evaluable stage IV rechallenged patients, best response was 1 CR, 3 SDs, and 5 PDs. 51/175 (29%) part 2 patients had a grade 1-4 irAE (11 [6%] with grade 3-4).

Conclusions: Pembrolizumab after crossover yielded a 39% ORR in evaluable patients and 3-yr PFS of ~32%. Pembrolizumab rechallenge had lower efficacy (11% ORR in evaluable patients).