Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

ATHENA (GOG-3020/ENGOT-ov45): a randomised, double-blind, placebo-controlled, phase 3 study of rucaparib + nivolumab following front-line platinum-based chemotherapy in ovarian cancer (#414)

Jeffrey C Goh 1 2 , Sally Baron-Hay 3 , Tony Bonaventura 4 , Martin Buck 5 , Andrew Dean 6 , Michael Friedlander 7 , Bo Gao 8 , Linda Mileshkin 9 , Martin K. Oehler 10 , Christopher Steer 11 , Vi Nguyen 12 , Sandra Goble 12 , Nikolay Grechko 12 , Bradley J. Monk 13 , Rebecca S. Kristeleit 14
  1. Royal Brisbane and Women’s Hospital, Brisbane, Australia
  2. University of Queensland, St Lucia, Australia
  3. Northern Cancer Institute – St Leonards, St Leonards, Australia
  4. Newcastle Private Hospital, New Lambton Heights, Australia
  5. Sir Charles Gairdner Hospital, Perth, Australia
  6. St John of God Subiaco Hospital, Subiaco, Australia
  7. Prince of Wales Private Hospital, Sydney, Australia
  8. Westmead Hospital, Westmead, Australia
  9. Peter MacCallum Cancer Center, Melbourne, Australia
  10. Burnside Hospital, Toorak Gardens, Australia
  11. Border Medical Oncology, Albury, Australia
  12. Clovis Oncology, Inc., Boulder, United States
  13. Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, United States
  14. University College London Cancer Institute, UCL, London, United Kingdom

Background: Ovarian tumours with homologous recombination deficiency (HRD) have a higher neoantigen load and expression of PD-1 and/or PD-L1 compared with ovarian tumours without HRD (Strickland et al. Oncotarget. 2016;7:13587-98). It is hypothesised that the increase in DNA damage caused by poly(ADP-ribose) polymerase (PARP) inhibition may result in a more antigenic tumour microenvironment in which an antitumour immune response can be stimulated. ATHENA (NCT03522246) is evaluating the PARP inhibitor rucaparib + the anti-PD-1 antibody nivolumab as maintenance treatment following front-line platinum-based chemotherapy in patients with newly diagnosed, high-grade ovarian, fallopian tube, or primary peritoneal cancer.

Trial Design: Patients will be enrolled at >270 sites worldwide, including in Australia. Eligible patients must have completed cytoreductive surgery (R0 permitted) prior to chemotherapy (primary surgery) or following neoadjuvant chemotherapy (interval debulking) and achieved an investigator-assessed response to first-line platinum-based doublet chemotherapy without disease progression or rising CA-125 at any time during first-line treatment. Approximately 1000 patients will be randomised 4:4:1:1 to Arm A (oral rucaparib 600 mg twice daily + IV nivolumab 480 mg on day 1 of every 4-week cycle), Arm B (oral rucaparib + IV placebo), Arm C (oral placebo + IV nivolumab), or Arm D (oral placebo + IV placebo). Stratification factors include centrally determined tumour HRD status (BRCA mutant, non-BRCA mutant/loss of heterozygosity [LOH] high, non-BRCA mutant/LOH low, or non-BRCA mutant/LOH unknown), posttreatment disease status (residual disease vs no residual disease), and timing of surgery (primary vs interval debulking). The primary endpoint of investigator-assessed progression-free survival (PFS; per RECIST v1.1) will be evaluated in 3 independent comparisons between arms: A vs B, A vs D, and B vs D. Secondary endpoints include blinded independent central review of PFS, overall survival, and safety.