EMA validates Jemperli marketing authorisation

GSK PLC

24 June 2024

 

Issued: 24 June 2024, London UK

Jemperli (dostarlimab) plus chemotherapy application accepted for review by the European Medicines Agency to expand use to all patients with primary advanced or recurrent endometrial cancer

·      Regulatory submission supported by statistically significant and clinically meaningful progression-free and overall survival data from Part 1 of the phase III RUBY trial

·      Dostarlimab plus chemotherapy is the only immuno-oncology-based therapy to show a statistically significant and clinically meaningful overall survival benefit in the broader patient population

 

GSK plc (LSE/NYSE: GSK) today announced the European Medicines Agency (EMA) has accepted its application to expand the use of Jemperli (dostarlimab) in combination with standard-of-care chemotherapy (carboplatin and paclitaxel) to all adult patients with primary advanced or recurrent endometrial cancer. The EMA's Committee for Medicinal Products for Human Use will begin the formal review process to make a recommendation to the European Commission, with approval expected in H1 2025.

Currently, in the EU, Jemperli in combination with carboplatin and paclitaxel is approved for the treatment of 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 this new application is approved, dostarlimab would be expanded to all patients with primary advanced or recurrent endometrial cancer, regardless of their biomarker type, including those with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours where currently there are no approved frontline immuno-therapy-based treatments in the EU.

The application is based on results from Part 1 of the RUBY phase III trial. The trial met its primary endpoints of investigator-assessed progression-free survival (PFS) and overall survival (OS), demonstrating a statistically significant and clinically meaningful benefit in the overall population of patients treated with dostarlimab plus carboplatin-paclitaxel versus chemotherapy alone. RUBY Part 1 is the only clinical trial to show a statistically significant overall survival 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.

OS data were presented at the Society of Gynecologic Oncology Annual Meeting on Women's Cancer on 16 March 2024[1], and were published in Annals of Oncology on 9 June 2024[2]. 

About endometrial cancer 

Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynaecologic cancer in developed countries, with approximately 417,000 new cases reported each year worldwide[3], and incidence rates are expected to rise by almost 40% between 2020 and 2040.[4]^,[5] In Europe, approximately 121,000 people are estimated to be diagnosed with primary advanced or recurrent endometrial cancer each year.[6] Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.[7] Among patients with primary advanced or recurrent endometrial cancer, approximately 70-75% have MMRp/MSS tumours.[8]

About RUBY 

RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of 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 investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the dMMR/MSI-H and overall populations and OS in the overall population. Pre-specified exploratory analyses of PFS and OS in the MMRp/MSS population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma.

In Part 2, the primary endpoint is investigator-assessed PFS in the overall population, followed by PFS in the MMRp/MSS population, and OS in the overall population is a key secondary endpoint. Additional secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.

RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organisation dedicated to transforming the standard of care in gynaecologic oncology.

About Jemperli (dostarlimab) 
Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK's ongoing immuno-oncology-based research and development programme. A robust clinical trial programme includes studies of Jemperli alone and in combination with other therapies in gynaecologic, colorectal and lung cancers, as well as where there are other opportunities for transformational outcomes. It was the first immuno-oncology treatment approved, in combination with chemotherapy, in the frontline setting for primary advanced or recurrent dMMR/MSI-H endometrial cancer.

In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is dMMR, as determined by a US FDA-approved test, or MSI-H, and as a single agent for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. The sBLA supporting this indication in combination with carboplatin and paclitaxel for dMMR/MSI-H primary advanced or recurrent endometrial cancer received Breakthrough Therapy designation and Priority Review from the US FDA. Jemperli is also indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 

Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli, and cobolimab (GSK4069889), a TIM-3 antagonist. 

Important Information for Jemperli in the EU

Indication

Jemperli is indicated:

-     in combination with carboplatin-paclitaxel, for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy;

-     as monotherapy for treating adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.

Refer to the Jemperli EMA Reference Information for a full list of adverse events and the complete important safety information in the EU here: https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli.

GSK in oncology

Oncology is an emerging therapeutic area for GSK where we are committed to maximising patient survival with a current focus on haematologic malignancies, gynaecologic cancers and other solid tumours through breakthroughs immune-oncology and tumour-cell targeting therapies.

About GSK

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.

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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D "Risk factors" in GSK's Annual Report on Form 20-F for 2023, and GSK's Q1 Results for 2024.

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[1] https://www.gsk.com/en-gb/media/press-releases/positive-ruby-phase-iii-data-show-potential-for-jemperli-dostarlimab-combinations-in-more-patients-with-primary-advanced-or-recurrent-endometrial-cancer/

[2] Powell MA, Bjørge L, Willmott L, et al. Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial, Annals of Oncology.2024. doi: https:// doi.org/10.1016/j.annonc.2024.05.546.

[3] Faizan U, Muppidi V. Uterine Cancer. [Updated 2022 Sep 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available at: www.ncbi.nlm.nih.gov/books/NBK562313/.

[4] Braun MM, et al. Am Fam Physician. 2016;93(6):468-474.

[5] International Research on Cancer. Global Cancer Observatory. Cancer Tomorrow. gco.iarc.fr/tomorrow/en/dataviz/. Accessed 13 July 2022.

[6] 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.

[7] CMP: CancerMPact® Patient Metrics Mar-2023, Cerner Enviza. Available at www.cancermpact.com. Accessed 29 Feb 2024.

[8] Based on CMP:CancerMPact® [Patient Metrics], Cerner Enviza. Available from www.cancermpact.com. Accessed 01 Mar 2024.

 

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