Abstract
Introduction/BackgroundRucaparib 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.MethodologyEligible 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.ResultsPatients (n≈1000) will be enrolled at >270 sites worldwide.ConclusionATHENA is evaluating rucaparib + nivolumab as frontline maintenance treatment in patients with OC.DisclosureAO: 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.