GSK's Jemperli/Chemo Combo: A Game Changer in Advanced Endometrial Cancer Treatment

The European Medicines Agency (EMA) has expanded the approval of GlaxoSmithKline's (GSK) Jemperli (dostarlimab) in combination with chemotherapy for the first-line treatment of adult patients with primary advanced or recurrent endometrial cancer who are candidates for systemic therapy. This approval broadens the previous indication for Jemperli plus chemotherapy in the European Union (EU) to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours, which represent approximately 75% of patients diagnosed with endometrial cancer and who have limited treatment options.



Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, commented on the approval: "For the first time, all patients with primary advanced or recurrent endometrial cancer in the EU have an approved immuno-oncology-based treatment that has shown a statistically significant and clinically meaningful overall survival benefit. We’re proud Jemperli continues to redefine the treatment landscape for patients."

Dr. Mansoor Raza Mirza, Chief Oncologist, Copenhagen University Hospital, Denmark, and RUBY principal investigator, added: "Clinicians have been waiting for years for an immuno-oncology-based option that can meaningfully improve overall survival outcomes for patients with MMRp/MSS primary advanced or recurrent endometrial cancer. The expanded approval represents a significant advance that delivers on this hope, now for patients with both dMMR/MSI-H and MMRp/MSS tumours."

The European Commission’s approval to expand the use of Jemperli plus chemotherapy is based on results from Part 1 of the RUBY phase III trial. RUBY Part 1 is the only clinical trial in this setting to show a clinically meaningful and statistically significant overall survival (OS) benefit in the full population of patients with primary advanced or recurrent endometrial cancer, demonstrating a 31% reduction in risk of death (HR: 0.69; 95% CI: 0.54–0.89) compared to chemotherapy alone.

At the 2.5-year landmark, the chance of being alive was 61% (95% CI: 54-67) for patients in the Jemperli plus chemotherapy group (245 patients) compared to 49% (95% CI: 43-55) in the chemotherapy group (249 patients). In addition, a 16.4-month improvement in median OS was observed with Jemperli plus chemotherapy versus chemotherapy alone (44.6 months [95% CI: 32.6–NR] vs. 28.2 months [95% CI: 22.1–35.6], respectively). The median duration of follow-up was more than three years.

The safety and tolerability analysis from RUBY Part 1 showed a safety profile for Jemperli plus carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse reactions (≥ 10%) in patients receiving Jemperli plus chemotherapy were rash, rash maculopapular, hypothyroidism, pyrexia, alanine aminotransferase increased, aspartate aminotransferase increased, and dry skin.

OS data were presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer on 16 March 2024, and were published in Annals of Oncology on 9 June 2024. The label for Jemperli plus chemotherapy in the US was expanded to all adult patients with primary advanced or recurrent endometrial cancer in August 2024.

Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. It is the most common gynaecologic cancer in developed countries, with an estimated 1.6 million people living with active disease at any stage and 417,000 new cases reported each year worldwide. Incidence rates are expected to rise by approximately 40% between 2020 and 2040. In Europe, approximately 121,000 people are estimated to be diagnosed with primary advanced or recurrent endometrial cancer each year. Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis. Among patients with primary advanced or recurrent endometrial cancer, approximately 75% have MMRp/MSS tumours.

RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of 785 patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.

In Part 1, the dual-primary endpoints are

The expanded approval of GSK's Jemperli in combination with chemotherapy for the treatment of primary advanced or recurrent endometrial cancer in the EU has significant implications for patients, healthcare providers, and the pharmaceutical industry. With this approval, a larger patient population now has access to an immuno-oncology-based treatment that has shown a statistically significant and clinically meaningful overall survival benefit. This approval also positions GSK to potentially capture a larger share of the endometrial cancer treatment market, as it can now compete for patients with MMRp/MSS tumours, which represent a significant portion of the patient population. Additionally, the improved survival rates and expanded patient population may lead to increased revenue for GSK, further solidifying its position in the global pharmaceutical market.