Tesaro release positive results from the GARNET study on dostarlimab in endometrial cancer.
TESARO, an oncology-focused business acquired by GlaxoSmithKline plc, presents data from the Phase 1/2 GARNET study evaluating dostarlimab in women with recurrent or advanced endometrial cancer who progressed on or after a platinum-based regimen.
These data were presented at the 2019 Society for Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer in Honolulu, Hawaii. The preliminary results demonstrate clinically meaningful and durable response rates of dostarlimab (anti-PD-1 antibody, formerly TSR-042), in this patient population, regardless of microsatellite instability status. In addition, the safety findings indicate that dostarlimab is well tolerated with a safety profile consistent with what is expected of anti-PD-1 therapy.
Further data from the GARNET study will be analysed using the RECIST 1.1 criteria to support regulatory filing for dostarlimab in endometrial cancer at the end of 2019.
Endometrial cancer (EC) is the most common gynaecologic malignancy in the U.S. There are limited treatment options for women whose disease progresses on or after first-line therapy. EC can be classified as microsatellite stable (MSS/75%) or microsatellite instability-high (MSI-H/25%). Currently, there is only one approved therapy in the recurrent EC setting for the subset of patients with MSI-H tumours, and no approved treatments for patients with MSS EC who have recurred after platinum-based chemotherapy.
A total of 125 patients were analysed including 41 MSI-H, and 79 MSS patients, as well as 5 with an unknown MSI-status. Dostarlimab was dosed at 500 mg once every 3 weeks for 4 doses, followed by 1000 mg once every 6 weeks until disease progression. Treatment with dostarlimab monotherapy resulted in a clinically meaningful response rate in recurrent or advanced EC who progressed on or after a platinum-based regimen, regardless of MSI status. Overall response rates by irRECIST in the full population, MSI-H population, and MSS population were 30%, 49%, and 20%, respectively. Disease control rate in the full population, MSI-H population, and MSS population was 53%, 63% and 47%, respectively.
At the time of data cutoff, treatment was still ongoing in 84% of responders, with 89% of the responders (33 of 37) having been on treatment for more than six months and 49% of responders (18 of 37) having been on treatment for more than one year. Durability of response was similar between the MSI-H and MSS cohorts. The median duration of response (DOR) has not yet been reached.
“We intend to use these data from the GARNET study to seek regulatory approval of dostarlimab to address the critical unmet treatment needs of women whose disease has progressed.”
The data show that 88 out of 125 patients had at least 1 treatment-emergent adverse event (TEAE). The most commonly reported TEAEs related to dostarlimab were fatigue, diarrhoea, and nausea.
Dostarlimab (TSR-042) is an investigational humanised anti-programmed death (PD)-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and effectively blocks its interaction with the ligands PD-L1 and PD-L2. If approved, dostarlimab would be the first anti PD-1 therapy administered as monotherapy every 3 weeks for 4 doses then every 6 weeks thereafter. Dostarlimab was developed as part of a collaboration between TESARO and AnaptysBio, Inc.
Dostarlimab is not currently approved for use anywhere in the world.
Mary Lynne Hedley, Ph.D., President and Chief Operating Officer of TESARO, said, “Currently, treatment options for women with advanced or recurrent endometrial cancer are limited, with only one FDA-approved agent for a subset of these patients. We intend to use these and other data from the GARNET study to seek regulatory approval of dostarlimab to potentially address the critical unmet treatment needs of women whose disease has progressed. The data presented today evaluating dostarlimab in women with recurrent/advanced endometrial cancer, combined with earlier data in patients with non-small cell lung cancer, reinforces the potential of dostarlimab in treating patients with a variety of solid tumours.”