CARIO-HPCA and Cooperative Gynecological Cancer Research Group (GINECO), Plerin, France
Anne-Claire Hardy-Bessard , Kathleen N. Moore , Mansoor Raza Mirza , Bernard Asselain , Andres Redondo , Jacobus Pfisterer , Sandro Pignata , Diane M. Provencher , David Cibula , Anna K.L. Reyners , Lubomir Bodnar , Rosalind Margaret Glasspool , Christos A. Papadimitriou , Rami Eitan , Sileny Han , Linda R. Duska , Bj Rimel , Sebastien Hazard , Jian Chen , Eric Pujade-Lauraine
Background: Despite surgery and SOC therapy (paclitaxel and carboplatin ± bevacizumab[bev]), 5-year survival rates remain low for patients (pts) with FIGO stage 3/4 OC. Niraparib (ZEJULA) is the first selective poly(ADP-ribose) polymerase inhibitor (PARPi) approved in the US and Europe for maintenance treatment in pts with recurrent OC regardless of BRCAmut status. Preclinical data suggest synergy with PARPi + anti-PD-1 blockade. Niraparib + pembrolizumab has shown clinical efficacy in pts with platinum-resistant or secondary refractory OC regardless of biomarker status. Dostarlimab is an anti–PD-1 humanized monoclonal with clinical activity as monotherapy in early phase trials. The primary objective of the currently enrolling FIRST trial is to compare PFS (per RECIST v1.1) in pts treated with SOC + dostarlimab + niraparib to SOC. Methods: Eligible pts (up to 912) are FIGO stage 3 (with residual disease, CC0 high risk, or planned neoadjuvant therapy) or stage 4, non-mucinous epithelial OC and ECOG score < 2. After 1 cycle of SOC, pts are stratified by concurrent bev use, BRCAmut/HRR status, and disease burden then randomized as 1:1:2 to 1 of 3 arms (Table). An innovative feature of ENGOT-OV44/FIRST (NCT03602859; EUDRACT 2018-000413-20) is the pre-planned adaptive study design to adapt the control arm to the evolving SOCs in OC, allowing pts in the control arm to receive up to date SOC. These adaptations will occur when practice-changing data are released. Following publication of SOLO1 results, BRCAmut pts will only be randomized to arm 2 or 3 to ensure they receive niraparib. Further adaptations may be incorporated as new data become available, leading to stop randomization in arm 1 or 2 of pts based on their biomarker status. Clinical trial information: NCT03602859
Treatment period | Initial Randomization Scheme | ||
---|---|---|---|
Arm 1* | Arm 2 | Arm 3 | |
Chemotherapy | SOC + IV placebo | SOC + IV placebo | SOC + IV dostarlimab |
Maintenance up to 3 years | Oral placebo + IV placebo | Oral niraparib + IV placebo | Oral niraparib + IV dostarlimab |
*No BRCAmut pts will be randomized to arm 1 following SOLO1 results.
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Abstract Disclosures
2020 ASCO Virtual Scientific Program
First Author: Anne-Claire Hardy-Bessard
2022 ASCO Genitourinary Cancers Symposium
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2019 ASCO Annual Meeting
First Author: Ignace Vergote
2022 ASCO Annual Meeting
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