EMA Accepts GSK’s Application for Use of Jemperli Plus Chemotherapy for All Endometrial Cancer Patients

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The European Medicines Agency (EMA) has accepted an application filed by GSK seeking expansion of the use of Jemperli (dostarlimab) in combination with standard-of-care chemotherapy (carboplatin and paclitaxel) to treat all adult patients with primary advanced or recurrent endometrial cancer. The EMA’s Committee for Medicinal Products for Human Use is expected to start the formal review process to make a recommendation to the European Commission, and approval is expected in the first half of 2025, according to a June 24, 2024 GSK company press release.

In the European Union (EU), Jemperli in combination with carboplatin and paclitaxel is currently approved for treating adult patients who are candidates for systemic therapy with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H). If approved under the new application, dostarlimab would be expanded to treating all patients with primary advanced or recurrent endometrial cancer. Treatment would be administered regardless of the patients’ biomarker type, including those with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors, where currently no approved frontline immuno-therapy-based treatments are available in the EU, according to GSK in the press release.

GSK’s application is based on results from Part 1 of a Phase III trial (RUBY), in which the primary endpoint was met—investigator-assessed progression-free survival and overall survival (OS), which demonstrated a statistically significant and clinically meaningful benefit in the overall patient population treated with dostarlimab plus carboplatin-paclitaxel compared to chemotherapy alone. According to the company press release, this trial is the only clinical trial that has shown a statistically significant OS benefit in this patient population. “The safety and tolerability analyses from RUBY showed a safety profile for dostarlimab plus carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents,” GSK stated in the release.

Endometrial cancer is found in the endometrium (inner lining of the uterus) and is the most common gynecologic cancer in developed countries. Approximately 417,000 new cases are reported each year worldwide (1) with incidence rates expected to increase by almost 40% between 2020 and 2040 (2,3). Approximately 121,000 people are estimated to be diagnosed with primary advanced or recurrent endometrial cancer yearly in Europe (4).

Jemperli, which was discovered by AnaptysBio, was licensed to TESARO in March 2014 (5); in December 2018, GSK announced its acquisition of TESARO in a $5.1 billion deal (6). Therefore, under the agreement with AnaptysBio, GSK is responsible for the ongoing research, development, commercialization, and manufacturing of Jemperli as well as another monoclonal antibody, cobolimab (GSK4069889), a T-cell immunoglobulin and mucin domain-containing protein 3 antagonist.

Jemperli is a programmed cell death receptor-1-blocking antibody; it forms the backbone of GSK’s immuno-oncology-based R&D program, according to the company press release. The company is carrying out a robust clinical trial program for Jemperli, including studies of Jemperli alone and in combination with other therapies in gynecologic, colorectal, and lung cancers. In the United States, Jemperli is approved in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent, for treating adult patients with primary advanced or recurrent endometrial cancer that is dMMR, as determined by a FDA-approved test, or MSI-H. Separately, it is approved as a single agent to treat adult patients with dMMR-recurrent or advanced endometrial cancer, as determined by a FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and who are not candidates for curative surgery or radiation. Jemperli is also indicated in the US for treating patients with dMMR recurrent or advanced solid tumors, as determined by a FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.

Meanwile in the EU, Jemperli is indicated in combination with carboplatin-paclitaxel for treating adult patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy, and as monotherapy for treating adult patients with dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.

References

1. Faizan, U.; Muppidi, V. Uterine Cancer (Archived) [Updated Sep 4, 2023]. In StatPearls [Internet]; StatPearls Publishing, 2024.
2. Braun M. M.; Overbeek-Wager, E. A.; Grumbo, R. J. Diagnosis and Management of Endometrial Cancer. Am. Fam. Physician. 2016, 93 (6), 468–474.
3. International Research on Cancer. Global Cancer Observatory. Cancer Tomorrow. gco.iarc.who.int/tomorrow/en (accessed July 1, 2024).
4. Concin, N.; Matias-Guiu, X.; Vergote, I.; et al. ESGO/ESTRO/ESP Guidelines for the Management of Patients with Endometrial Carcinoma. International Journal of Gynecologic Cancer 2021, 31, 12–39.
5. AnaptysBio. Anaptysbio and Tesaro Announce Strategic Immuno-Oncology Antibody Collaboration. Press Release, March 13, 2024.
6. GSK. GSK Reaches Agreement to Acquire TESARO, an Oncology Focused Biopharmaceutical Company. Press Release, Dec. 3, 2018.

Source: GSK