A randomized, double-blind, placebo-controlled multicenter phase 3 trial of niraparib maintenance treatment in patients with advanced ovarian cancer following frontline chemotherapy

Abstract

Background: Niraparib (ZEJULA™) is a selective poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor. In preclinical studies, niraparib concentrated in the tumor vs plasma, delivering ≥90% durable PARP 1/2 inhibition and a persistent antitumor effect. In the ENGOT-OV16/NOVA trial, niraparib demonstrated clinical efficacy in patients with recurrent ovarian cancer (OC) following complete response (CR) or partial response (PR) to platinum-based chemotherapy (PBC) regardless of BRCA mutation or homologous recombination deficiency (HRD) status. Trial design: The primary objective of the ongoing ENGOT-OV26/PRIMA trial is efficacy (measured as progression-free survival) of niraparib vs placebo in advanced OC patients with CR or PR following frontline PBC. Secondary objectives include overall survival, patient-reported outcomes (PROs), time to first subsequent therapy, time to progression on the next anticancer therapy, and safety and tolerability of niraparib. Target enrollment is ≈330 patients with stage III or IV OC with PR or CR after PBC. Eligibility criteria include all patients with stage IV disease and patients with stage III disease who were treated with neoadjuvant chemotherapy followed by interval debulking surgery or who have either inoperable disease or visible residual disease after primary debulking surgery. Patients are stratified based on HRD status (HRD positive, including the known deleterious BRCA mutations gBRCAmut or sBRCAmut/HRD negative), neoadjuvant chemotherapy (yes/no), and best response to PBC (CR/PR). Patients are randomized 2:1 to oral niraparib 300 mg or matched placebo once daily in 28-day cycles. PRO data will be collected.