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P116 ATHENA (GOG-3020/ENGOT-ov45; EudraCT 2017–004557–17; NCT03522246): a randomised, double-blind, placebo-controlled, phase 3 study of the poly(ADP-Ribose) polymerase (PARP) inhibitor rucaparib + the PD-1 inhibitor nivolumab following frontline platinum-based chemotherapy in ovarian cancer (OC)
  1. A Christopoulou1,
  2. F Marmé2,
  3. A Oaknin3,
  4. D Lorusso4,
  5. T Safra5,
  6. G Lindahl6,
  7. A Chudecka-Glaz7,
  8. T Ciuleanu8,
  9. DC Collins9,
  10. F Demirkiran10,
  11. I Lifrenko11,
  12. T Van Gorp12,
  13. RL Coleman13,
  14. K Fujiwara14,
  15. AM Oza15,
  16. SN Westin13,
  17. DM O’Malley16,
  18. TJ Herzog17,
  19. R Eskander18,
  20. M Wilson19,
  21. S Argire20,
  22. N Grechko20,
  23. IA McNeish21,
  24. BJ Monk22 and
  25. RS Kristeleit23
  1. 1Medical Oncology Unit, St Andrews General Hospital of Patras, Patras, Greece
  2. 2Gynäkologische Onkologie, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany
  3. 3Medical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
  4. 4Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  5. 5Sourasky Medical Center, Tel Aviv, Israel
  6. 6Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
  7. 7Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University in Szczecin, Szczecin, Poland
  8. 8Iuliu Haţieganu University of Medicine and Pharmacy and Ion Chiricuta Institute of Oncology, Cluj-Napoca, Romania
  9. 9Cork University Hospital, Cork, Ireland
  10. 10Department OBandGYN, Division of Gynecologic Oncology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
  11. 11Kursk Regional Oncology Dispensary, Kursk, Russian Federation
  12. 12University of Leuven, Leuven, Belgium
  13. 13Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  14. 14Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan
  15. 15Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
  16. 16Clinical Research Gynecologic Oncology, The Ohio State University, James Cancer Center, Columbus
  17. 17Department of Ob/Gyn, University of Cincinnati Cancer Institute, University of Cincinnati, Cincinnati, OH
  18. 18Department of Reproductive Medicine Division of Gynecologic Oncology, Rebecca and John Moores Cancer Center, University of California, La Jolla, CA, USA
  19. 19Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand
  20. 20Clinical Operations, Clovis Oncology UK Ltd., Cambridge
  21. 21Department of Surgery and Cancer, Imperial College London, London, UK
  22. 22Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ, USA
  23. 23Academic Department of Oncology, University College London Cancer Institute, UCL, London, UK


Introduction/Background Rucaparib has clinical activity in patients with recurrent OC with or without homologous recombination (HR) deficiency (HRD; eg, a BRCA mutation or high genomic loss of heterozygosity [LOH]) and is hypothesised to provide clinical benefit following frontline treatment. ATHENA is evaluating rucaparib + nivolumab as maintenance treatment following frontline platinum-based chemotherapy in patients with newly diagnosed, high-grade ovarian, fallopian tube, or primary peritoneal cancer. The rationale for this combination includes: tumours with BRCA mutations express tumour-specific proteins (neoantigens), which attract PD-L1-expressing, tumour-infiltrating lymphocytes; ovarian tumours with HRD have more neoantigens relative to HR-proficient tumours and may respond to immune checkpoint inhibitors; rucaparib combined with anti-PD-1 demonstrated improved antitumour activity in an OC model; it is hypothesised that PARP inhibitor-induced DNA damage may increase neoantigens, regardless of HRD status.

Methodology Eligible patients must have completed frontline platinum-doublet chemotherapy and surgery and achieved an investigator-assessed response without disease progression or rising CA-125 at any time during frontline treatment. Cytoreductive surgery (R0 permitted) could have been completed prior to chemotherapy or following neoadjuvant chemotherapy. Patients will be randomised 4:4:1:1 to receive maintenance treatment in Arm A (oral rucaparib 600 mg BID + intravenous nivolumab 480 mg Q4W), Arm B (oral rucaparib + intravenous placebo), Arm C (oral placebo + intravenous nivolumab), or Arm D (oral placebo + intravenous placebo). Stratification factors include centrally determined tumour HRD status (BRCA mutant, non-BRCA mutant/LOH high, non-BRCA mutant/LOH low, or non-BRCA mutant/LOH indeterminate), posttreatment disease status, and timing of surgery. Investigator-assessed progression-free survival (RECIST v1.1; primary endpoint) will be compared between arms. Secondary endpoints include blinded independent central review of progression-free survival, overall survival, objective response rate, and safety.

Results Patients (n≈1000) will be enrolled at >270 sites worldwide.

Conclusion ATHENA is evaluating rucaparib + nivolumab as frontline maintenance treatment in patients with OC.

Disclosure AO: Clovis, AstraZeneca, Genmab/Seattle Genetics, ImmunoGen, PharmaMar, Roche, Tesaro DL: Clovis, AstraZeneca, ImmunoGen, Merck, PharmaMar, Roche, Tesaro DC: AstraZeneca, Genmab, Pfizer, Seattle Genetics, BMS, MSD, Roche RLC: Clovis, AbbVie, AstraZeneca, Esperance, Janssen, Millennium, Merck, OncoMed, Roche/Genentech, Bayer, GamaMabs, Genmab, Gradalis, Pfizer, Tesaro KF: Advanced Oncotherapy, AstraZeneca, Chugai-Roche, Daiichi-Sankyo, Eisai, GSK, ImmunoGen, Kaken-Seiyaku, Lilly, Merck, Ono Pharmaceutical, Pfizer, Shionogi, Taiho, Zeria Pharmaceutical AMO: Clovis, Amgen, Immunovaccine, Verastem, AstraZeneca, WebRx SNW: Clovis, AstraZeneca, Bio Ascend, Genentech, Gynecologic Oncology Group, Medivation/Pfizer, Merck, Ovation, Roche, Takeda, Tesaro, Vermillion, ArQule, Bayer, Cotinga Pharmaceuticals, Novartis DMO’M: Clovis, AstraZeneca, Gynecologic Oncology Group, Janssen, Myriad, Tesaro, Amgen, ImmunoGen, AbbVie, Health Analytics, Ambry, Agenus, Ajinomoto, Array BioPharma, BMS, ERGOMED Clinical Research, Exelixis, Genentech, GSK, INC Research, inVentiv Health Clinical, Ludwig Institute for Cancer Research, Novartis, PRA International, Regeneron, Serono, Stemcentrx, TRACON TJH: Clovis, AstraZeneca, Caris, Johnson & Johnson, Roche, Tesaro RE: Clovis, AstraZeneca, Roche/Genentech, Merck, Pfizer, Tesaro MW: AstraZeneca, MSD, Roche SA, NG: Clovis IAM: Clovis, AstraZeneca, Tesaro BJM: Clovis, AstraZeneca, Janssen/Johnson & Johnson, Myriad, Roche/Genentech, Tesaro, Amgen, Bayer, Biodesix, Cerulean, GSK, Gradalis, ImmunoGen, Insys, Mateon, Merck, NuCana, Perthera, Pfizer, Precision Oncology, Verastem, Vermillion RSK: Clovis, Tesaro, Roche All other authors have nothing to disclose.

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