2022-RA-1638-ESGO Randomized Phase III Trial on Niraparib-TSR-042 (dostarlimab) Versus Physician’s Choice in Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment: NItCHE Trial (MITO 33)

Introduction/Background Platinum resistant ovarian cancer patients have a poor prognosis, and few treatment options are available. Preclinical and clinical data demonstrated that the combination of poly-ADP ribose polymerase inhibitors (PARPi) with immune checkpoint inhibitors (ICIs) could have a synergistic antitumor activity in this setting of patients. MITO 33 trial will assess the hypothesis that the combination niraparib/dostarlimab therapy is effective in increasing overall survival, progression free survival and time to first subsequent therapy with respect to chemotherapy alone. Methodology Patients will be randomized 1:1 to receive:Arm A (physician’s choice chemotherapy): pegylated liposomal doxorubicin 40 mg/mq d1q28, weekly paclitaxel 80 mg/mq d1,8,15q28, gemcitabine 1000 mg/mq d1,8,15q28 or topotecan 1.25 mg/mq d1–5q21;Arm B (dostarlimab + niraparib): dostarlimab 500 mg every 3 weeks for 4 cycles, then 1000 mg every 6 weeks + niraparib 300 mg or 200 mg daily.Patients will be stratified according to homologous recombination deficiency status (positive vs negative), PD-L1 status, previous immunotherapy, previous PARPi treatment and Bevacizumab therapy. Homologous Recombination Deficiency status will be evaluated with Foundation One CDx test and tumor PD-L1 expression will be evaluated on archival pre-therapy lesion. Results Inclusion Criteria- Recurrent platinum resistant epithelial ovarian, fallopian tube or primary peritoneal cancer (no more than 2 previous chemotherapy lines)- Previous treatment with PARPi and/or ICIs are allowed (if at least 6 months from last treatment have intercurred)- Conclusion Primary Endpoint Overall SurvivalSecondary Endpoints: Progression Free Survival; Time to First Subsequent Therapy and Objective Response Rate; Safety and Tolerability of Dostarlimab plus Niraparib