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

Year: 2018

Session type: Poster / e-Poster / Silent Theatre session

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.