Dostarlimab plus chemotherapy is the only immuno-oncology combination to show statistically significant and clinically meaningful overall survival (OS) in the overall population
31% reduction in risk of death and 16.4-month improvement in median OS observed with dostarlimab plus chemotherapy versus chemotherapy in the overall population
37% reduction in risk of disease progression or death and 6-month improvement in median progression-free survival observed with the addition of Zejula (niraparib) to dostarlimab maintenance following dostarlimab plus chemotherapy versus chemotherapy in MMRp/MSS population where treatment options are still needed
16 March 2024--GSK plc (LSE/NYSE: GSK) today announced statistically significant and clinically meaningful overall survival (OS) results from Part 1 and progression-free survival (PFS) results from Part 2 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial in adult patients with primary advanced or recurrent endometrial cancer. These data were presented today in a late-breaking plenary session at the Society of Gynecologic Oncology 2024 Annual Meeting on Women’s Cancer (16-18 March).
The goal of the RUBY phase III trial programme is to evaluate which patients with primary advanced or recurrent endometrial cancer could potentially benefit from treatment with Jemperli (dostarlimab) plus chemotherapy, with or without the addition of Zejula (niraparib) maintenance. Part 1 of the RUBY phase III trial is investigating dostarlimab plus standard-of-care chemotherapy (carboplatin-paclitaxel) followed by dostarlimab compared to chemotherapy plus placebo followed by placebo. Part 2 of the RUBY phase III trial is evaluating dostarlimab plus standard-of-care chemotherapy, followed by dostarlimab plus niraparib as maintenance therapy compared to chemotherapy plus placebo followed by placebo. The safety and tolerability profiles of dostarlimab plus carboplatin-paclitaxel and dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib were generally consistent with the known safety profiles of the individual medicines.
Previous data showed a statistically significant and clinically meaningful improvement in PFS with Jemperli plus chemotherapy versus chemotherapy alone in frontline mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer. These data led to regulatory approvals for this patient population in the US, EU and certain other countries. Data presented today show additional potential benefit of dostarlimab plus chemotherapy, with or without the addition of niraparib, in the overall population of patients with primary advanced or recurrent endometrial cancer, including patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours, for which there are currently no approved immuno-therapy-based regimens.
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK said: “The positive data presented today further show how dostarlimab-based regimens could benefit a broader set of patients with endometrial cancer. The results we’ve seen to date comprise the growing body of evidence supporting the role of dostarlimab as the backbone of our immuno-oncology development programme. Our goal is to continue to identify ways to use dostarlimab alone and in combination with other therapies to help improve outcomes for patients with limited treatment options.”
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 worldwide1, and incidence rates are expected to rise by almost 40% between 2020 and 2040.2,3 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.4
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 is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2.5
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 supplemental Biologics License Application supporting the newly approved 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.
About Zejula (niraparib)
Zejula is an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor indicated in the US for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy; and for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy and who have been selected based on a US FDA-approved companion diagnostic for Zejula.
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.
References
1.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/.
2.Braun MM, et al. Am Fam Physician. 2016;93(6):468-474.
3.International Research on Cancer. Global Cancer Observatory. Cancer Tomorrow. gco.iarc.fr/tomorrow/en/dataviz/. Accessed 13 July 2022.
4.CMP: CancerMPact® Patient Metrics Mar-2023, Cerner Enviza. Available at www.cancermpact.com. Accessed 29 Feb 2024.
5.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.