FDA Approves Dostarlimab in Advanced dMMR/MSI-H Endometrial Cancer

“Based on the results from the RUBY clinical trial, I look forward to the addition of [dostarlimab] to chemotherapy becoming a new standard of care for patients," according to principal investigator Matthew Powell, MD, chief of the Division of Gynecologic Oncology at Washington University School of Medicine.

The FDA has approved dostarlimab (Jemperli) plus carboplatin and paclitaxel with subsequent single-agent dostarlimab as a frontline treatment option for patients with primary advanced or recurrent mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) endometrial cancer, according to a press release from GSK.¹

Patients with dMMR disease, as determined through an FDA-approved test, are eligible to receive dostarlimab.

Supporting data for the approval came from the phase 3 RUBY/ENGOT-EN6/GOG3031/NSGO trial (NCT03981796).

According to findings presented at The Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and subsequently published in New England Journal of Medicine,^2,3 dostarlimab plus chemotherapy elicited a 24-month progression-free survival (PFS) rate of 36.1% (95% CI, 29.3%-42.9%) vs 18.1% (95% CI, 13%-23.9%) with placebo plus chemotherapy (HR, 0.64; 95% CI, 0.51-0.80; P <.001). In the dMMR/MSI-H population, the estimated 24-month PFS rate was 61.4% (95% CI, 46.3%-73.4%) vs 15.7% (95% CI, 7.2%-27.0%) in each respective arm (HR, 0.28; 95% CI, 0.16-0.50; P <.001).

The safety profile of dostarlimab in the RUBY trial was comparable with previous reports.¹ The most common treatment-emergent adverse effects (TEAEs), occurring in at least 20% of patients, included rash, diarrhea, hypothyroidism, and hypertension.

“As a clinician, I celebrate the practice-changing potential of adding [dostarlimab] to chemotherapy for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer who have had limited treatment options,” principal investigator Matthew Powell, MD, chief of the Division of Gynecologic Oncology at Washington University School of Medicine, said in the press release.¹ “Based on the results from the RUBY clinical trial, I look forward to the addition of [dostarlimab] to chemotherapy becoming a new standard of care for patients.”

In the global, double-blind, phase 3 RUBY trial, patients were randomly assigned to receive dostarlimab plus carboplatin and paclitaxel (n = 245) or placebo plus the same chemotherapy backbone (n = 249). Patients received 500 mg of dostarlimab or matched placebo plus 175 mg/m² of paclitaxel and carboplatin at area under the curve of 5 mg/mL per minute every 3 weeks for 6 cycles. Maintenance therapy consisted of 1000 mg of dostarlimab or matched placebo every 6 weeks for up to 3 years.

The primary end points were PFS per investigator assessment and overall survival. Secondary end points included overall response rate, duration of response, and disease control rate.

In June 2023, the FDA granted priority review to dostarlimab for the treatment of patients with dMMR/MSI-H advanced or recurrent endometrial cancer.⁴

In February 2023, the FDA granted regular approval to dostarlimab in this patient population following disease progression or receipt of prior platinum-based treatment for those who are not candidates for curative radiation or surgery.⁵

References

1. Jemperli (dostarlimab) plus chemotherapy approved in the US as the first new frontline treatment option in decades for dMMR/MSI-H primary advanced or recurrent endometrial cancer. News release. GSK. July 31, 2023. Accessed July 31, 2023. https://shorturl.at/izGL9
2. Mirza M, Chase D, Slomovitz, 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, Florida.
3. 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
4. GSK receives US FDA file acceptance for Jemperli (dostarlimab) plus chemotherapy for the treatment of dMMR/MSI-H primary advanced or recurrent endometrial cancer. News Release. GSK plc. June 6, 2023. Accessed July 31, 2023. https://bit.ly/43n9wBZ
5. FDA grants regular approval to dostarlimab-gxly for dMMR endometrial cancer. News release. FDA. February 9, 2023. Accessed June 6, 2023. http://bit.ly/3xbGuH2