Phase III RUBY clinical trial demonstrates potential of Jemperli + chemotherapy to redefine the treatment of primary advanced or recurrent endometrial cancer versus chemotherapy alone

A statistically significant and clinically meaningful improvement in progression free survival (PFS) was observed for dostarlimab plus carboplatin-paclitaxel in the mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) population (n=118) and in the overall population (n=494) versus placebo plus chemotherapy. The separation of the lines in the Kaplan-Meier curve below illustrates the significant reduction in risk of disease progression or death in patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer in the dostarlimab plus chemotherapy treatment arm compared to the placebo plus chemotherapy treatment arm.

Dr Mansoor Raza Mirza, Chief Oncologist, Copenhagen University Hospital, Denmark and RUBY principal investigator, said: “Clinical practice has been waiting decades for a meaningful advancement in the standard of care for primary advanced or recurrent endometrial cancer. The results from the RUBY clinical trial, especially given the difficult-to-treat histologies included in the trial, demonstrate support for a new treatment standard with the addition of dostarlimab to current standard-of-care chemotherapy.”

The safety and tolerability profile of dostarlimab in combination with carboplatin-paclitaxel in the RUBY phase III trial was generally consistent with the known safety profiles of the individual agents. The most common ( greater than 45%) treatment-emergent adverse events (TEAEs) in both treatment arms in the dMMR/MSI-H and overall populations were nausea, alopecia and fatigue, as well as anaemia in the placebo plus chemotherapy arm in the dMMR/MSI-H population. Severe and serious TEAEs were approximately 10% higher in the dostarlimab plus carboplatin-paclitaxel arm compared with the placebo plus carboplatin-paclitaxel arm in the overall population.

The nature and types of immune-related adverse events (irAEs) in the dostarlimab plus chemotherapy safety profile were consistent with the mechanism of action of dostarlimab and similar to those reported for other PD-(L)1 inhibitors. In the overall population, 38.2% of participants in the dostarlimab plus carboplatin-paclitaxel arm and 15.4% of participants in the placebo plus carboplatin-paclitaxel arm had irAEs assessed by the investigator as related to dostarlimab or placebo, respectively. The most frequently reported dostarlimab-related irAE categories were endocrinopathies (15.8% dostarlimab-related versus 3.3% placebo-related) and skin adverse reactions (14.1% dostarlimab-related versus 3.7% placebo-related). Discontinuation of dostarlimab or placebo due to a TEAE occurred in 17.4% of patients in the dostarlimab plus chemotherapy treatment arm and 9.3% of patients in the placebo plus chemotherapy treatment arm in the overall population.

These data were shared in a European Society for Medical Oncology (ESMO) Virtual Plenary, presented in a late breaking session at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer (25-28 March) and published simultaneously in The New England Journal of Medicine.

See-"Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer"- Mansoor R. Mirza, M.D., Dana M. Chase, M.D., Brian M. Slomovitz, M.D., René dePont Christensen, Ph.D., et al., for the RUBY Investigators-March 27, 2023. DOI: 10.1056/NEJMoa2216334.