Jemperli for Advanced Uterine/Endometrial Cancer

by Dr. C.H. Weaver M.D. updated 5/2025

Updated results from the RUBY trial presented at the 2025 SGO Annual Meeting on Women’s Cancer demonstrated that adding Jemperli to standard chemotherapy (carboplatin and paclitaxel) provides longer-lasting responses for patients with advanced or recurrent endometrial cancer, regardless of their tumor’s genetic profile. Data from the GARNET study demonstrated the potential of Jemperli (dostarlimab) immunotherapy to treat specific subsets of women with advanced endometrial cancer leading to FDA approval in April 2021,^2,6  and results from the Ruby clinical trial established Jemperli combined with chemotherapy as a new standard for patients with primary advanced or recurrent endometrial cancer.9,10 In August 2024, the FDA approved the combination of Jemperli with carboplatin and paclitaxel, followed by Jemperli alone, for the treatment of adult patients with primary advanced or recurrent endometrial cancer, irrespective of MMR or MSS status.

Endometrial cancer (Uterine) is the most common gynecologic malignancy in the U.S. but there have been limited treatment options for women whose disease progresses on or after first-line therapy until recently.

Microsatellite instability (MSI) is the condition of genetic hypermutability or a predisposition to mutations in cells that results from the bodies impaired DNA mismatch repair (MMR) mechanism. DNA MMR is an essential function and the way the body naturally corrects errors that spontaneously occur during cell division associated DNA replication.

Mismatch Repair Genes work like genetic “spell checkers.” When problems occur in these spell-checking MMR genes, it means that areas of DNA start to become unstable and the body is unable to correct the errors that occur during DNA replication and consequently accumulate errors. The accumulation of errors causes the creation of novel microsatellite fragments that can be measured. The presence of MSI represents evidence that the MMR function is not working normally and predisposition to developing cancer exists. 

Endometrial cancers may have MSI-H or dMMR identified when NGS testing is performed. EC can be classified as microsatellite stable (MSS/75%) or microsatellite instability-high (MSI-H/25%) and until recently no effective treatments were currently available for either group.

About Jemperli (dostarlimab)

Jemperli is a humanized anti-programmed death (PD)-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and effectively blocks its interaction with the ligands PD-L1 and PD-L2. Jemperli precision cancer immunotherapy helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD -L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade an attack by the body’s immune cells. Jemperli works similar to other checkpoint inhibitors.

Key Study Findings From GARNET

A total of 125 women with recurrent EC were treated with Jemperli 500 mg once every 3 weeks for 4 doses, followed by 1000 mg once every 6 weeks until disease progression. In the initial analyses patients were categorized as MSI-H (33%), MSS (63%) and unknown MSI-status (4%).

Treatment with Jemperli resulted in a clinically meaningful response rate in recurrent EC who progressed on or after a platinum-based regimen regardless of MSI status. The overall response rates in the MSI-H population, and MSS population was 53%, 63% and 47%, respectively. At the time of data cutoff, treatment was still ongoing in 84% of responders, with 89% of the responders (33 of 37) having been on treatment for more than six months and 49% of responders (18 of 37) having been on treatment for more than one year.

An updated analysis included patients with dMMR EC; Treatment with Jemperli showed an a response rate of 42% and a disease control rate of 58%. Overall, 13% of patients had a complete response and 30% of patients had a partial response. At the time of data cutoff, with a median follow up of 11.2 months ongoing responses were reported for up to 20 months.

The Ruby Clinical Trial

Updated results from the RUBY trial presented at the 2025 SGO Annual Meeting on Women’s Cancer demonstrated that adding Jemperli to standard chemotherapy (carboplatin and paclitaxel) provides longer-lasting responses for patients with advanced or recurrent endometrial cancer, regardless of their tumor’s genetic profile.

Key Findings

• Longer Duration of Response:
  Patients receiving Jemperli plus chemotherapy had a median response duration of 10.6 months, compared to 6.2 months for those receiving chemotherapy with placebo—a difference of 4.4 months.
• More Patients Responded for 2 Years or Longer:
  37% of patients on Jemperli plus chemotherapy maintained their response for at least 24 months, compared to just 14.3% in the placebo group.
• Benefits Seen Across All Patient Groups:
  • Mismatch Repair-Proficient (pMMR/MSS): Median response lasted 8.6 months with Jemperli vs. 6.3 months with placebo.
  • Mismatch Repair-Deficient (dMMR/MSI-H): The median response was not reached (over 10.1 months) with Jemperli, vs. 5.4 months with placebo. Over half (62.2%) of these patients maintained their response for at least 24 months.

Survival Improvements

• Overall Survival:
  Patients treated with Jemperli plus chemotherapy had a median overall survival of 44.6 months, compared to 28.2 months for those on placebo plus chemotherapy.
• Progression-Free Survival:
  Median time before the cancer worsened was 11.8 months with Jemperli vs. 7.9 months with placebo.

Safety

• Side Effects:
  Most side effects were manageable and included hypothyroidism, joint pain, skin rash, and increased liver enzymes. Few patients experienced serious immune-related side effects after two years of treatment.

What This Means for Patients

These results support the use of Jemperli plus chemotherapy as a new standard of care for all patients with advanced or recurrent endometrial cancer, offering hope for longer-lasting responses and improved survival.

References:

1. Data from GARNET study indicates robust activity of dostarlimab in patients with advanced or recurrent endometrial cancer
2. A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients with Advanced Solid Tumors (GARNET). ClinicalTrials.gov.. Accessed February 2020.
3. Oaknin A, Duska LR, Sullivan RJ, et al. Preliminary safety, efficacy, and pharmacokinetic/pharmacodynamic characterization from GARNET, a phase I/II clinical trial of the anti–PD-1 monoclonal antibody, TSR-042, in patients with recurrent or advanced MSI-H and MSS endometrial cancer. Presented at 2019 SGO Annual Meeting; March 16-19, 2019; Honolulu, HI. Abstract 33.
4. Laken H, Kehry M, Mcneeley P, et al. Identification and characterization of TSR-042, a novel anti-human PD-1 therapeutic antibody. European Journal of Cancer. 2016;69,S102. doi:10.1016/s0959-8049(16)32902-1.
5. A Study of Dostarlimab (TSR-042) Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Patients with Recurrent or Primary Advanced Endometrial Cancer (RUBY). ClinicalTrials.gov.. Accessed February 2020.
6. https://www.gsk.com/en-gb/media/press-releases/fda-grants-accelerated-approval-for-gsk-s-jemperli-dostarlimab-gxly-for-women-with-recurrent-or-advanced-dmmr-endometrial-cancer/

7. The RUBY phase III trial met its primary endpoint in a planned interim analysis in patients with primary advanced or recurrent endometrial cancer. News release. GSK. December 2, 2022. Accessed December 2, 2022. https://bit.ly/3H1XEgl

8. A study to evaluate dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in participants with recurrent or primary advanced endometrial cancer (RUBY). ClinicalTrials.gov. Updated August 12, 2022. Accessed December 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03981796

9. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab in combination with chemotherapy for the treatment of primary advanced or recurrent endometrial cancer: a placebo-controlled randomized phase 3 trial (ENGOT-EN6-NSGO/GOG-3031/RUBY). Presented at: 2023 SGO Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, FL.

10. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. Published online March 27, 2023. doi:10.1056/NEJMoa2216334.Mirza MR, Willmott LJ, Hietanen S, et al. Updated duration of response for patients receiving dostarlimab plus carboplatin-paclitaxel treatment compared with patients receiving placebo plus carboplatin-paclitaxel in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial. Presented at: 2025 SGO Annual Meeting on Women’s Cancer. March 14-17, 2025; Seattle, Washington. Poster 232.