OBJECTIVES: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial. METHODS: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with blinded independent central review, sensitivity analyses of the source-verified population compared with the randomized population, and analysis of safety in this population were completed. RESULTS: In total, 118 patients with dMMR/MSI-H were enrolled in the RUBY trial (53, dostarlimab arm; 65, placebo arm). At the first interim analysis, a 72% reduction in the risk of progression or death (P < 0.0001) was seen with dostarlimab plus carboplatin-paclitaxel by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), which was consistent with blinded independent central review per RECIST v1.1. Likewise, sensitivity analyses of the source-verified dMMR/MSI-H population compared with the randomized dMMR/MSI-H population were consistent for progression-free survival and overall survival. Safety results seen in the dMMR/MSI-H population were similar to those previously reported for the overall population. CONCLUSIONS: All primary and secondary efficacy assessments demonstrate the consistent benefit of dostarlimab plus carboplatin-paclitaxel. The improvements seen in survival and the manageable safety profile support the favorable benefit-risk profile for dostarlimab plus carboplatin-paclitaxel in patients with dMMR/MSI-H primary advanced or recurrent EC.

Arizona Center for Cancer Care Phoenix AZ USA

Baptist MD Anderson Cancer Center Jacksonville FL USA

David Geffen School of Medicine at UCLA Los Angeles CA USA

Department of Clinical Oncology Zealand University Hospital Roskilde and University of Copenhagen Copenhagen Denmark

Department of Gynaecology Obstetrics and Neonatology General University Hospital Prague 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Gynecologic Oncology University of Cincinnati Medical Center Cincinnati OH USA

Department of Medical Oncology Catharina Hospital Eindhoven the Netherlands

Department of Medical Oncology Erasmus MC Cancer Institute University Medical Center Rotterdam the Netherlands

Department of Obstetrics and Gynecology LSU Health Shreveport and Willis Knighton Physician Network Shreveport LA USA

Department of Obstetrics Gynecology AMITA Health Adventist Medical Center Hinsdale IL USA

Department of Obstetrics Gynecology and Women's Health Montefiore Medical Center Albert Einstein College of Medicine Bronx NY USA

Department of Oncology Rigshopitalet Copenhagen University Hospital Copenhagen and Nordic Society of Gynaecological Oncology Clinical Trial Unit Copenhagen Denmark

Diakoneo Diak Klinikum Schwäbisch Hall and Department of Women's Health Tuebingen University Hospital Tuebingen Germany

Division of Gynecologic Oncology McGill University Health Centre Women's Health Research Unit Research Institute McGill University Health Centre Gerald Bronfman Department of Oncology McGill University Montreal QC Canada

Division of Gynecologic Oncology Norris Cotton Cancer Center Dartmouth Hitchcock Medical Center Lebanon NH USA

Division of Gynecologic Oncology St Vincent Indianapolis Hospital Indianapolis IN USA

Georgia Cancer Center Augusta University Augusta GA USA

GSK Collegeville PA USA

GSK London UK

Gynecologic Oncology Arizona Oncology Tucson AZ USA

Hanjani Institute for Gynecologic Oncology Abington Hospital Jefferson Health Asplundh Cancer Pavilion Sidney Kimmel Medical College of Thomas Jefferson University Willow Grove PA USA

Karolinska University Hospital Solna Sweden

Medical Oncology IRCCS Regina Elena National Cancer Institute Rome Italy

National Cancer Institute sponsored NRG Oncology Washington University School of Medicine St Louis MO USA

Oklahoma Cancer Specialists and Research Institute Tulsa OK USA

St Joseph's Candler Gynecologic Oncology and Surgical Specialists Candler Hospital Savannah GA USA

The Ohio State University and The James Comprehensive Cancer Center Columbus OH USA

University of Virginia Health System Charlottesville VA USA

Washington University School of Medicine Washington University in St Louis St Louis MO USA

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