A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer

Official Title

ENGOT-0V44 The FIRST (First-line Ovarian Cancer Treatment With Niraparib Plus TSR-042) Study: A Randomized, Double-blind, Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer

Summary:

Ovarian cancer is a heterogeneous disease, characterized by complex molecular and genetic changes. The high expression of vascular endothelial growth factor (VEGF) receptor, programmed death receptor ligands 1 (PD-L1) expression, and deoxyribonucleic acid (DNA) damage in ovarian tumours provide several targets for treatment and maintenance of disease response. Given the unmet medical need of participants with advanced or metastatic ovarian cancer, this study design will enable investigators to provide participants with current SOC for ovarian cancer for the duration of the study. This is a global, multicentre, randomized, double-blind, controlled Phase 3 study that will primarily compare progressive survival rate of PD-L1 positive patients and also to compare progression-free survival (PFS) of all participants with Stage III or IV high-grade nonmucinous epithelial ovarian cancer treated with platinum-based combination therapy, dostarlimab, and niraparib to SOC platinum-based combination therapy. The currently recommended SOC therapy for the first line treatment of Stage III or IV ovarian cancer is the combination of paclitaxel and carboplatin, with or without concurrent and maintenance bevacizumab. Participants will receive SOC during the chemotherapy Run-In period (cycle 1) before randomization to study treatment (cycle 2). Concurrent bevacizumab use must be determined prior to randomization at cycle 2. Approximately 1228 participants will be enrolled into the study and the duration of the study will be approximately 78 months.

Trial Description

Primary Outcome:

  • PFS for PD-L1 positive participants
  • PFS for all participants
Secondary Outcome:
  • Blinded Independent Central Review (BICR) for PD-L1 positive participants
  • BICR for all the participants
  • PFS per investigator-assessed immune-related of PD-L1 positive participants
  • PFS per investigator-assessed immune-related for all the participants
  • Overall Survival (OS) of PD-L1 positive participants
  • OS of all the participants
  • Number of PD-L1 positive participants with treatment-emergent adverse events (TEAEs)
  • Number of overall participants with TEAEs
  • Number of PD-L1 positive participants with serious adverse events (SAEs)
  • Number of overall participants with SAEs
  • Number of PD-L1 positive participants with treatment discontinuations or dose delays or dose reductions due to adverse events
  • Number of all the participants with treatment discontinuations or dose delays or dose reductions due to adverse events
  • Number of PD-L1 positive participants with immune-related adverse events of interest (irAEIs)
  • Number of all the participants with irAEIs
  • Number of PD-L1 positive participants with changes in Eastern Cooperative Oncology Group (ECOG) performance status
  • Number of overall participants with changes in ECOG performance status
  • Number of PD-L1 positive participants with abnormal hematology results
  • Number of all the participants with abnormal hematology results
  • Number of PD-L1 positive participants with abnormal blood chemistry results
  • Number of all the participants with abnormal blood chemistry results
  • Change from Baseline in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) assessment among PD-L1 positive participants
  • Change from Baseline in the EQ-5D-5L assessment among all participants
  • Change from Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) assessment among PD-L1 positive participants
  • Change from Baseline in the EORTC-QLQ-C30 assessment among all the participants
  • Change from Baseline in the EORTC-QLQ Ovarian Cancer Module OV28 (EORTC-QLQ-OV28) assessment among PD-L1 positive participants
  • Change from Baseline in the EORTC-QLQ-OV28 assessment among all the participants
  • Time to symptom worsening in the EQ-5D-5L assessment among the PD-L1 positive participants
  • Time to symptom worsening in the EQ-5D-5L assessment among all the participants
  • Time to symptom worsening in the EORTC-QLQ-C30 assessment among the PD-L1 positive participants
  • Time to symptom worsening in the EORTC QLQ-C30 assessment among all the participants
  • Time to symptom worsening in the EORTC-QLQ-OV28 assessment among the PD-L1 positive participants
  • Time to symptom worsening in the EORTC-QLQ-OV28 assessment among all the participants
  • Time to first subsequent therapy (TFST) in PD-L1 positive participants
  • TFST in all the participants
  • Time to second subsequent therapy (TSST) in PD-L1 positive participants
  • TSST in all the participants
  • Time to progression on next-line therapy (PFS2,) in PD-L1 positive participants
  • PFS2 in all the participants
  • Objective Response Rate (ORR) among PD-L1 positive participants
  • ORR among all the participants
  • Pathologic complete response (pCR) rate among PD-L1 positive participants
  • pCR rate among all the participants
  • Duration of response (DOR) in PD-L1 positive participants
  • DOR in all the participants
  • Disease control rate (DCR) in PD-L1 positive participants
  • DCR in all the participants
  • Maintenance progression-free survival (MPFS) in PD-L1 positive participants
  • MPFS in all the participants

View this trial on ClinicalTrials.gov

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Resources

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