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.