Abstract 1887
Background
Most pts with advanced OC will experience recurrence within 2 years of initial platinum-based treatment. An unmet need exists for therapies that delay disease recurrence. Niraparib (Zejula®) is a selective poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor approved for maintenance in pts with recurrent OC regardless of BRCA or homologous recombination deficiency (HRD) status. Bev is a VEGF inhibitor approved in OC for treatment and maintenance therapy. Targeted therapies + VEGF inhibition showed synergy in preclinical models. Induction of intratumoural hypoxia downregulating BRCA and RAD51 may sensitize tumours to PARP inhibition and lead to apoptosis via contextual synthetic lethality. Niraparib + bev is being explored in the treatment setting in the ongoing phase 1/2 AVANOVA trial, which has shown that niraparib can be safely combined with bev. In OVARIO, niraparib + bev will be evaluated in the maintenance setting in pts with advanced OC who have recovered from primary debulking surgery and responded to frontline platinum-based chemo with bev.
Trial design
Target enrolment is 90 pts, regardless of BRCA or HRD status, with stage 3b and 4 epithelial ovarian, fallopian tube, or peritoneal cancer. Pts must achieve complete or partial response or no evidence of disease after frontline platinum-based chemo with bev. The starting dose of niraparib will be based on baseline body weight and/or platelet count. Pts weighing ≥77 kg with a platelet count of ≥ 150,000/μL will receive 300 mg qd. Pts weighing <77 kg or with a platelet count of < 150,000/μL will receive 200 mg qd. The bev dosage will be 15 mg/kg q3w up to 15 months. Pts will be treated continuously until disease progression or unacceptable toxicity. The primary objective for OVARIO is progression-free survival at 18 months. Secondary objectives include overall survival, time to first subsequent therapy, and safety and tolerability.
Clinical trial identification
NCT03326193.
Legal entity responsible for the study
Tesaro, Inc.
Funding
Tesaro, Inc.
Editorial Acknowledgement
Writing and editorial support, funded by Tesaro, Inc. (Waltham, MA, USA) and coordinated by Hemant Vyas, PhD of Tesaro, Inc., was provided by Nicole Renner, PhD and Mary Kacillas of Ashfield Healthcare Communications (Middletown, CT, USA).
Disclosure
J.M. Hope: Stock and other ownership interests: Alaska Cyberknife Center. J. Chen, M. Wainszelbaum, D. Gupta: Employment, stock and other ownership interests: Tesaro, Inc. All other authors have declared no conflicts of interest.
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