Safety and efficacy of the anti-PD-1 monoclonal antibody dostarlimab in patients with recurrent or advanced dMMR endometrial cancer

Objectives Dostarlimab (TSR-042) is a humanized programmed death (PD)-1 receptor monoclonal antibody that blocks interaction with PD-1 ligands, PD-L1 and PD-L2. The objective of this interim analysis was to assess the safety and efficacy of dostarlimab in patients with mismatch repair deficient (dMMR) endometrial cancer (EC) who enrolled in the GARNET trial (NCT02715284).

Materials and Methods The trial enrolled patients with immunohistochemistry-confirmed dMMR EC with recurrent/advanced disease that progressed on a platinum-doublet regimen. Patients received 500 mg Q3W of dostarlimab for 4 cycles, then 1000 mg Q6W until disease progression/discontinuation. Primary endpoints were objective response rate (ORR) and duration of response (DOR) as assessed against Response Evaluation Criteria in Solid Tumors v1.1 by blinded independent central review.

Results As of the data cutoff, 104 patients with dMMR EC were enrolled and dosed. Of these, 71 had measurable disease at baseline and ≥6 months of follow-up. The confirmed ORR was 42.3% (95% CI, 30.6%-54.6%); confirmed complete and partial response rates were 12.7% and 29.6%, respectively. Responses were durable; the median DOR was not reached (median follow-up was 11.2 months). The estimated likelihood of maintaining response at 6 and 12 months was 96.4% and 76.8%, respectively. Anemia (2.9%), colitis (1.9%), and diarrhea (1.9%) were the most common grade ≥3 treatment-related adverse events. There were no deaths assessed as related to dostarlimab treatment.

Summary Preliminary data for dostarlimab demonstrated clinical activity in patients with previously treated recurrent or advanced dMMR EC with an acceptable safety profile.

Sponsor GlaxoSmithKline, Waltham, MA, USA

 

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Interessenkonflikt

Lars Christian Hanker has nothing to disclose. A. Oaknin reports Consulting and Honoraria from AstraZeneca, Tesaro, Clovis, PharmaMar, and Roche outside the submitted work. Tinker reports grants and personal fees from AstraZeneca outside the submitted work. Lucy Gilbert reports personal fees from Merck, AstraZeneca, and Pfizer outside the submitted work. V. Samouëlian has nothing to disclose. C. Mathews reports institutional reimbursement for costs associated with the study from Tesaro. J. Brown reports honoraria fees from Olympus; consulting or advisory role fees from Caris, Tesaro, Clovis, AstraZeneca and Genentech; and speakers’ bureau fees from Clovis outside the submitted work. W. Guo is an employee of GlaxoSmithKline. H. Danaee Employee of GlaxoSmithKline. E. Im is an employee of GlaxoSmithKline. R. Sabatier reports grants from EISAI; personal fees and non-financial support from Roche and Pfizer; personal fees from TESARO and NOVARTIS; grants, personal fees and non-financial support from Astra-Zeneca; and non-financial support from AMGEN outside the submitted work. All other authors declare that they have no conflict of interest.

Publication History

Article published online:
07 October 2020