Efficacy and safety of dostarlimab in combination with chemotherapy in patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer in a phase 3, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY)

Matthew A Powell; David Cibula; David M O'Malley; Ingrid Boere; Mark S Shahin; Antonella Savarese; Dana M Chase; Lucy Gilbert; Destin Black; Jørn Herrstedt; Sudarshan Sharma; Stefan Kommoss; Michael A Gold; Anna M Thijs; Kari Ring; Magnus Frödin Bolling; Joseph Buscema; Sarah E Gill; Paul Nowicki; Nicole Nevadunsky; Michael Callahan; Lyndsay Willmott; Carolyn McCourt; Caroline Billingsley; Sharad A Ghamande; Zangdong He; Morad Marco Balas; Shadi Stevens; Evelyn Fleming; Mansoor Raza Mirza

doi:10.1016/j.ygyno.2024.10.022

Efficacy and safety of dostarlimab in combination with chemotherapy in patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer in a phase 3, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY)

Gynecol Oncol. 2024 Nov 11:192:40-49. doi: 10.1016/j.ygyno.2024.10.022. Online ahead of print.

Authors

Matthew A Powell¹, David Cibula², David M O'Malley³, Ingrid Boere⁴, Mark S Shahin⁵, Antonella Savarese⁶, Dana M Chase⁷, Lucy Gilbert⁸, Destin Black⁹, Jørn Herrstedt¹⁰, Sudarshan Sharma¹¹, Stefan Kommoss¹², Michael A Gold¹³, Anna M Thijs¹⁴, Kari Ring¹⁵, Magnus Frödin Bolling¹⁶, Joseph Buscema¹⁷, Sarah E Gill¹⁸, Paul Nowicki¹⁹, Nicole Nevadunsky²⁰, Michael Callahan²¹, Lyndsay Willmott²², Carolyn McCourt²³, Caroline Billingsley²⁴, Sharad A Ghamande²⁵, Zangdong He²⁶, Morad Marco Balas²⁶, Shadi Stevens²⁷, Evelyn Fleming²⁸, Mansoor Raza Mirza²⁹

Affiliations

¹ National Cancer Institute-sponsored NRG Oncology, Washington University School of Medicine, St Louis, MO, USA. Electronic address: mpowell@wustl.edu.
² Department of Gynaecology, Obstetrics and Neonatology, General University Hospital in Prague, First Faculty of Medicine, Charles University, Prague, Czech Republic.
³ The Ohio State University and The James Comprehensive Cancer Center, Columbus, OH, USA.
⁴ Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, the Netherlands.
⁵ Hanjani Institute for Gynecologic Oncology, Abington Hospital-Jefferson Health, Asplundh Cancer Pavilion, Sidney Kimmel Medical College of Thomas Jefferson University, Willow Grove, PA, USA.
⁶ Medical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
⁷ David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁸ 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.
⁹ Department of Obstetrics and Gynecology, LSU Health Shreveport, and Willis-Knighton Physician Network, Shreveport, LA, USA.
¹⁰ Department of Clinical Oncology, Zealand University Hospital Roskilde and University of Copenhagen, Copenhagen, Denmark.
¹¹ Department of Obstetrics/Gynecology, AMITA Health Adventist Medical Center, Hinsdale, IL, USA.
¹² Diakoneo Diak Klinikum, Schwäbisch Hall, and Department of Women's Health, Tuebingen University Hospital, Tuebingen, Germany.
¹³ Oklahoma Cancer Specialists and Research Institute, Tulsa, OK, USA.
¹⁴ Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands.
¹⁵ University of Virginia Health System, Charlottesville, VA, USA.
¹⁶ Karolinska University Hospital, Solna, Sweden.
¹⁷ Gynecologic Oncology, Arizona Oncology, Tucson, AZ, USA.
¹⁸ St Joseph's/Candler Gynecologic Oncology & Surgical Specialists, Candler Hospital, Savannah, GA, USA.
¹⁹ Baptist MD Anderson Cancer Center, Jacksonville, FL, USA.
²⁰ Department of Obstetrics, Gynecology, and Women's Health, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
²¹ Division of Gynecologic Oncology, St Vincent Indianapolis Hospital, Indianapolis, IN, USA.
²² Arizona Center for Cancer Care, Phoenix, AZ, USA.
²³ Washington University School of Medicine, Washington University in St Louis, St Louis, MO, USA.
²⁴ Department of Gynecologic Oncology, University of Cincinnati Medical Center, Cincinnati, OH, USA.
²⁵ Georgia Cancer Center, Augusta University, Augusta, GA, USA.
²⁶ GSK, Collegeville, PA, USA.
²⁷ GSK, London, UK.
²⁸ Division of Gynecologic Oncology, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
²⁹ Department of Oncology, Rigshopitalet, Copenhagen University Hospital, Copenhagen, and Nordic Society of Gynaecological Oncology-Clinical Trial Unit, Copenhagen, Denmark.

PMID: 39531903
DOI: 10.1016/j.ygyno.2024.10.022

Abstract

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.

Keywords: Dostarlimab plus chemotherapy; Endometrial cancer; Immunotherapy plus chemotherapy; Primary advanced or recurrent endometrial cancer; dMMR/MSI-H endometrial cancer.