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


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Rebecca S. Kristeleit1,Iain A. McNeish2,Roshan Agarwal3,Susana Banerjee4,Clare Barlow5,Michelle Ferguson6,Maxine Flubacher7,Marcia Hall8,Rebecca Herbertson9,Jane Hook10,Rachel Jones11,Louise Li12,Fiona Lofts13,Rowan E. Miller14,Sarah Moon15,Shibani Nicum16,Fiona Nussey17,Christine Parkinson18,Justin Waters19,Isabella Capobianco20,Sandra Goble20,Nikolay Grechko20,Bradley J. Monk21
1University College London Cancer Institute, UCL,2Imperial College London,3Northampton General Hospital,4The Royal Marsden NHS Foundation Trust,5Musgrove Park Hospital,6Ninewells Hospital & Medical School,7Poole Hospital NHS Foundation Trust,8Mount Vernon Cancer Centre,9Royal Sussex County Hospital,10St James’s University Hospital,11South West Wales Cancer Centre,12The James Cook University Hospital,13St George’s Hospital,14St. Bartholomew's Hospital, Barts Health NHS Trust,15Morecombe Bay NHS Trust, Lancaster,16Oxford Cancer Centre,17Edinburgh Cancer Centre, Western General Hospital,18Addenbrookes Hospital, Cambridge,19East Kent Hospitals University NHS Foundation Trust,20Clovis Oncology, Inc.,21Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine

Abstract

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.

Method

Eligible patients must have completed cytoreductive surgery 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. Enrolled 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 (per RECIST v1.1) will be evaluated in 3 independent comparisons between arms: A vs B, A vs D, and B vs D.

Results

Approximately 1000 patients will be enrolled at >220 sites worldwide, including in the United Kingdom.

Conclusion

ATHENA will evaluate rucaparib + nivolumab as first-line maintenance treatment in patients with ovarian cancer.