ENGOT-Ov41/GEICO-69-O/ANITA trial: A phase III randomized, double-blinded trial of platinum-based chemotherapy (CT) with or without atezolizumab (ATZ) followed by niraparib maintenance with or without ATZ in patients with recurrent ovarian, tubal or peritoneal cancer (OC) and platinum treatment-free interval (TFIp) >6 months.

Abstract

TPS5599 Background: Platinum-based CT is the treatment of choice for OC patients (pts) with TFIp > 6 months suitable for platinum. Niraparib is an oral PARP inhibitor that significantly prolongs the progression-free survival (PFS) of OC pts when given as maintenance therapy after a response to platinum-rechallenge (both in gBRCA and non-gBRCA mutated pts). Atz is a humanized monoclonal antibody targeting PD-L1 that showed activity in heavily pretreated OC pts. Combination of anti-PD-L1 and CT may improve the activity of the anti-PD-L1 antibody by increasing the amount of antigens released after immunogenic cell death induced by CT. Combination of PARPi and anti-PD-L1/PD-1 has shown synergy in preclinical models and promising clinical activity in certain indications. Methods: ANITA (NCT03598270) is a phase III, randomized (1:1), double-blinded, multi-center study to assess the efficacy of the addition of Atz to platinum-based doublet CT followed by maintenance niraparib in patients with recurrent high grade serous or endometrioid OC with a TFIp > 6 months. Approximately 414 patients with ECOG 0-1, known BRCA status, at least one measurable lesion and ≤ 2 prior lines will be randomized to placebo of Atz (Arm A) or Atz (Arm B) in combination with one of three possible standard platinum-based CT regimens (investigator’s choice) followed by maintenance niraparib in combination with placebo or Atz, according to randomization, if experiencing response or stable disease by RECIST after CT. Stratification factors: 1) Platinum-based regimen (paclitaxel-carboplatin vs gemcitabine-carboplatin vs PLD-carboplatin); 2) Platinum-free interval (6-12 vs > 12 months); and 3) BRCA status (mutated vs non-mutated). Dose of Atz is 1200 mg q3 weeks or 840 mg q2 weeks depending on the platinum-based regimen selected. Niraparib initial dose (300 vs 200 mg) is decided based on body weight and platelet counts after CT according to RADAR analysis. Primary endpoint is PFS based on investigator assessment by RECIST v1.1. Clinical trial information: NCT03598270.