ENGOT-OV44/FIRST study: A randomized, double-blind, adaptive, phase III study of platinum-based therapy with dostarlimab (TSR-042) + niraparib versus standard-of-care (SOC) platinum-based therapy as first-line treatment of stage 3/4 non-mucinous epithelial ovarian cancer (OC).

person Anne-Claire Hardy-Bessard CARIO-HPCA and Cooperative Gynecological Cancer Research Group (GINECO), Plerin, France info_outline 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

Authors person Anne-Claire Hardy-Bessard CARIO-HPCA and Cooperative Gynecological Cancer Research Group (GINECO), Plerin, France info_outline 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 Organizations CARIO-HPCA and Cooperative Gynecological Cancer Research Group (GINECO), Plerin, France, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, Nordic Society of Gynecologic Oncology (NSGO) and Rigshospitalet University Hospital, Copenhagen, Denmark, Institut Curie and GINECO, Paris, France, Hospital Universitario La Paz-IdiPAZ and Spanish Ovarian Cancer Research Group (GEICO), Madrid, Spain, AGO Study Group Germany, Gynecologic Oncology Center, Kiel, Germany, MITO- Italy, Division of Gynecologic Oncology, Instituto Nazionale Tumori-IRCCSS- Fondazione G. Pascale, Napoli, Italy, University of Montreal, Montreal, QC, Canada, CEECOG, Gynecologic Oncology Center-Department of Obstetrics and Gynecology-General University Hospital in Prague, Prague, Czech Republic, DGOG-Hollande, Groningen, Netherlands, PGOG, Military Institute of Medicine, Warsaw, Poland, SGCTG/NCRI-UK, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom, HeCOG-Greece, Aretaieio University Hospital, Athens, Greece, ISGO-Israel, Rabin Medical Center, Tel Aviv University, Petah Tikva, Israel, BGOG & Department of Gynaecology and Obstetrics, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium, University of Virginia, Charlottesville, VA, Cedar Sinai Medical Center, Los Angeles, CA, TESARO, Inc., Waltham, MA, ARCAGY-GINECO, Paris, France Abstract Disclosures Research Funding Pharmaceutical/Biotech Company 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 BRCA mut 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, BRCA mut/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, BRCA mut 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 BRCA mut pts will be randomized to arm 1 following SOLO1 results.