Methods
serous, toxicity, Cancer
ADVERSE EVENT, DISEASE, ADVERSE EVENT, CANCER
A multi-centre, open-label, two-stage, phase II study assessed niraparib monotherapy or in combination with dostarlimab in recurrent EC (NCT03016338). The study initially enrolled patients with recurrent EC to the niraparib monotherapy cohort (cohort 1—C1). Once C1 was completed, a sequential second cohort assessed niraparib in combination with dostarlimab (cohort 2—C2). Cross-over between cohorts was not permitted. The trial complied with all relevant ethical regulators. The protocol was approved by the Ontario Cancer, McGill University, Alberta Health Research Ethics Board, and Health Canada. All patients provided written informed consent. The study design and conduct complied with all relevant regulations regarding the use of human study participants and was conducted in accordance with the criteria set by the Declaration of Helsinki. There was no compensation for study participants. Enrollment occurred between the 17 November 2017 and 29 January 2019 in Cohort 1, and 2 October 2019 and 8 October 2020 in Cohort 2.Patients with recurrent serous or endometrioid EC were enrolled. There was no limit on prior lines of therapy, and prior platinum-based chemotherapy was required with no limitation on timing. Previous treatment with a PARP inhibitor, or other targeted therapy directed against the homologous recombination pathway was not allowed. Enrolled patients had an Eastern Cooperative Group (ECOG) performance status of ≤2. Within 7 days of the proposed start of treatment, patients had adequate organ and marrow function (protocol in supplementary note In the first cohort patients received niraparib 200 or 300 mg orally once daily, based on baseline body weight and platelet count, in a four-week cycle. In the second cohort niraparib (same dose and schedule) was given with dostarlimab 500 mg intravenously every three weeks for four cycles, followed by 1,000 mg every six weeks thereafter.The primary endpoint of the trial was clinical benefit rate (CBR) in the intention-to-treat population, which includes complete or partial response, or stable disease ≥16 weeks. Secondary endpoints included ORR, PFS, OS, and safety and tolerability assessment. Response assessment was performed per RECIST (Response Evaluation Criteria in Solid Tumours) v1.1 every eight weeks. All patients who initiated treatment were evaluable for safety and toxicity from first treatment dose. Adverse event (AE) grading was per the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Exploratory objectives included assessment of PTEN, MMR status and PD-L1 by IHC as a predictor of response to therapy, as well as the role of genes involved in the HRR pathway, 