GSK Presents New Data from the GARNET Study Demonstrating Potential of Dostarlimab to Treat a Subset of Women with Recurrent or Advanced Endometrial Cancer

GlaxoSmithKline plc (LSE/NYSE:GSK) today announced data from an updated analysis of the GARNET trial, which demonstrated that dostarlimab, an investigational anti-programmed death-1 (PD-1) monoclonal antibody, provided clinically meaningful results in women with recurrent or advanced mismatch repair-deficient (dMMR) endometrial cancer who progressed on or after a platinum-based regimen.

This updated analysis included patients with dMMR endometrial cancer who had measurable disease at baseline and =6 months of follow-up by the data cutoff (n=71). Patients received 500 mg of dostarlimab once every three weeks for four doses, followed by 1,000 mg once every six weeks until disease progression. The primary endpoints were confirmed objective response rate (ORR) and duration of response (DOR), as assessed against RECIST v 1.1 by blinded independent central review. GARNET is the largest dataset evaluating an anti-PD-1 in endometrial cancer.

Treatment with dostarlimab showed an ORR of 42% (95% CI; 31-55) and a disease control rate of 58% (95% CI; 45-69). Overall, 13% of patients had a complete response and 30% of patients had a partial response. At the time of data cutoff, with a median follow up of 11.2 months, the median DOR had not been reached (1.87+ to 19.61+ months).

Dr. Axel Hoos, Senior Vice President and Head Oncology R&D, GSK said: "We are committed to developing medicines for patients who face high unmet medical need. We believe in the clinical potential of dostarlimab for women with advanced or recurrent dMMR endometrial cancer who urgently need additional treatment options for this incurable disease.”

Dr. Ana Oaknin, Head of the Gynaecologic Cancer Program at Vall d’Hebron Institute of Oncology, Barcelona, and primary investigator for GARNET said: "There are limited treatment options for women with advanced or recurrent endometrial cancer, and prognosis of these patients is poor. The results observed in the GARNET trial indicate the potential of dostarlimab to offer a new treatment option for women with this challenging disease.”

The safety population included all patients with dMMR endometrial cancer who received at least one dose of dostarlimab (n=104). Results showed that dostarlimab was well tolerated with a low discontinuation rate (2%) due to treatment-related adverse events (TRAEs), consistent with the safety profiles of other anti-PD-1 therapies. The most commonly reported TRAEs were asthenia (15%), diarrhea (15%), fatigue (14%), and nausea (13%). No deaths associated with dostarlimab were reported in the study.

Dostarlimab is not currently approved for use anywhere in the world.

About GARNET
The ongoing phase I GARNET trial is evaluating dostarlimab as monotherapy in patients with advanced solid tumors. Part 2B of the study includes five expansion cohorts: dMMR/microsatellite instability-high (MSI-H) endometrial cancer (cohort A1), mismatch repair-proficient endometrial cancer (cohort A2), non-small cell lung cancer (cohort E), dMMR/MSI-H non-endometrial cancer (cohort F), and platinum-resistant ovarian cancer without BRCA mutations (cohort G). GARNET is still enrolling patients.^i,ii

About Dostarlimab
Dostarlimab is an investigational humanized anti-PD-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and blocks its interaction with the ligands PD-L1 and PD-L2.ⁱⁱⁱ

In addition to GARNET, dostarlimab is being investigated for women with recurrent or primary advanced endometrial cancer in combination with standard of care (chemotherapy) in the phase III RUBY trial.^iv Dostarlimab is also being evaluated in combination with other therapeutic agents for patients with advanced solid tumors or metastatic cancer.

About Endometrial Cancer^v
Endometrial cancer is a main type of uterine cancer that forms in the inner lining of the uterus, known as the endometrium. Endometrial cancer can be classified as mismatch repair-deficient/microsatellite instability-high or mismatch repair-proficient/microsatellite stable. There are limited treatment options for women whose disease progresses on or after first-line therapy. Endometrial cancer is the sixth most common cancer in women worldwide.^vi

GSK in Oncology
GSK is focused on maximizing patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics, and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilizing modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

About GSK
GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us.

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 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2019.

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ⁱ A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients with Advanced Solid Tumors (GARNET). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02715284. Accessed February 2020.
ⁱⁱ Oaknin A, Duska LR, Sullivan RJ, et al. Preliminary safety, efficacy, and pharmacokinetic/pharmacodynamic characterization from GARNET, a phase I/II clinical trial of the anti–PD-1 monoclonal antibody, TSR-042, in patients with recurrent or advanced MSI-H and MSS endometrial cancer. Presented at 2019 SGO Annual Meeting; March 16-19, 2019; Honolulu, HI. Abstract 33.
ⁱⁱⁱ 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.
^iv A Study of Dostarlimab (TSR-042) Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Patients with Recurrent or Primary Advanced Endometrial Cancer (RUBY). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03981796. Accessed February 2020.
^v Endometrial Cancer Treatment (PDQ®)– Health Professional Version. National Cancer Institute. https://www.cancer.gov/types/uterine/hp/endometrial-treatment-pdq. Accessed February 2020.
^vi Endometrial cancer. World Cancer Research Fund. https://www.wcrf.org/dietandcancer/endometrial-cancer. Published September 12, 2018. Accessed February 2020.

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