Randomized phase III trial on niraparib-TSR-042 (dostarlimab) versus physician's choice chemotherapy in recurrent ovarian, fallopian tube, or primary peritoneal cancer patients not candidate for platinum retreatment: NItCHE trial (MITO 33)

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 with immune checkpoint inhibitors could have a synergistic antitumor activity in this setting of patients. Primary Objective The primary objective is to assess the efficacy of niraparib plus dostarlimab compared with chemotherapy in recurrent ovarian cancer patients not suitable for platinum treatment. Study Hypothesis This trial will assess the hypothesis that niraparib plus dostarlimab therapy is effective to increase overall survival, progression--free survival, and time to first subsequent therapy respect to chemotherapy alone, with an acceptable toxicity profile. Trial Design This is a phase III, multicenter trial, where recurrent ovarian cancer patients not eligible for platinum re-treatment will be randomized 1:1 to receive niraparib plus dostarlimab vs physician's choice chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent. The study will be performed according to European Network for Gynaecological Oncological Trial groups (ENGOT) model B and patients will be recruited from 40 sites across MITO, CEEGOG, GINECO, HeCOG, MANGO, and NOGGO groups. Major Inclusion/Exclusion criteria Eligible patients must have recurrent epithelial ovarian cancer not eligible for platinum retreatment. Patients who received previous treatment with poly--ADP ribose polymerase inhibitors and/ or immune checkpoint inhibitors will be eligible. No more than two prior lines of treatment are allowed. Primary Endpoint The primary endpoint is overall survival defined as the time from the randomization to the date of death by any cause. Sample Size 427 patients will be randomized. Estimated Dates for Completing Accrual and Presenting Results June 2024