Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK, said: “Today’s expanded approval of Jemperli redefines the treatment landscape for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer. Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression. In the RUBY trial, Jemperli plus chemotherapy demonstrated a 71% reduction in the risk of disease progression or death versus chemotherapy in this patient population, providing a statistically significant and clinically meaningful benefit. These results and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.” Wenora Johnson, President, Board of Directors, Facing Our Risk of Cancer Empowered (FORCE) said: “The endometrial cancer community is thrilled by today’s news, which changes the treatment paradigm for a population with long-term unmet needs. FORCE is grateful for the many participants and researchers who contributed to this important study. As an endometrial cancer survivor, I know how much this approval offers hope for patients with primary advanced or recurrent dMMR/MSI-H endometrial cancer.” The FDA approval is supported by interim analysis results from Part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial, which reflect a robust median duration of follow-up of ≥ 25 months. The trial met the primary endpoint of investigator-assessed progression-free survival (PFS), demonstrating a statistically significant and clinically meaningful benefit in patients treated with Jemperli plus carboplatin and paclitaxel in the dMMR/MSI-H population. In the dMMR/MSI-H population, a 71% reduction in the risk of disease progression or death was observed. Part 1 of the RUBY trial continues to assess overall survival (OS) in the intent-to-treat (ITT) population, a dual-primary endpoint alongside investigator-assessed PFS. The RUBY trial data were presented at the European Society for Medical Oncology (ESMO) Virtual Plenary and Society of Gynecologic Oncology (SGO) Annual Meeting on 27 March 2023, and were simultaneously published in The New England Journal of Medicine.
The sBLA supporting this new indication was reviewed under the FDA Oncology Center of Excellence Project Orbis Framework, which allowed for concurrent submission to and review by US and other international regulatory authorities. As part of Project Orbis, the application remains under review in Australia, Canada, Switzerland, Singapore and the United Kingdom. A marketing authorisation application is also under review by the European Medicines Agency. The dual-primary endpoints in Part 1 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 ITT populations and OS in the overall population. Pre-specified exploratory analyses of PFS in the mismatch repair proficient (MMRp)/microsatellite stable (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. Secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability. 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 mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H), and as a single agent for adult patients with mismatch repair-deficient (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 the new indication in combination with carboplatin and paclitaxel received Breakthrough Therapy designation from the 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. The collaboration has resulted in three monospecific antibody therapies that have progressed into the clinic. These are: Jemperli (GSK4057190), a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of each of these medicines under the agreement. Please see accompanying US Prescribing Information.
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. [1] Faizan U, Muppidi V. Uterine Cancer. [Updated 2022 Sep 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available at: https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/books/NBK562313/. [2] American Cancer Society. Key Statistics For Endometrial Cancer. https://www.cancer.org/cancer/endometrial-cancer/about/key-statistics.html. Updated February 14, 2022. Accessed March 29, 2023. [3] Cerner Enviza CancerMPact® Patient Metrics 2022. CMP:CancerMPact® [Patient Metrics], Cerner Enviza. Available from www.cancermpact.com. Accessed 11 May 2023.
[4] CancerMPact® [Treatment Architecture], Cerner Enviza. Available from www.cancermpact.com. Accessed 11 May 2023.
[5] Cerner Enviza CancerMPact® [Treatment Architecture]. Available from www.cancermpact.com. Accessed 14 Apr 2023.
[6] Halla K. Emerging Treatment Options for Advanced or Recurrent Endometrial Cancer. J Adv Pract Oncol. 2022 Jan;13(1):45-59. doi: 10.6004/jadpro.2022.13.1.4. Epub 2022 Feb 1. PMID: 35173988; PMCID: PMC8805805. [7] Laken H, Kehry M, Mcneeley P, et al. Identification and characterization of TSR-042, a novel anti-human PD-1 therapeutic antibodyPD-1 therapeutic antibody. European Journal of Cancer. 2016;69,S102. doi:10.1016/s0959-8049(16)32902-1.