Dostarlimab Shows Strong Efficacy In The Treatment Of Advanced Or Recurrent Endometrial Cancer, With A Total Response Rate Of 42%!

- Mar 03, 2020-

GlaxoSmithKline (GSK) recently released the latest analysis data of the anti-PD-1 therapy dostarlimab (formerly known as TSR-042) Phase I / II clinical study GARNET. The results showed that in patients with recurrent or advanced mismatch repair defects (dMMR) endometrial cancer that progressed during or after platinum-containing chemotherapy, dostarlimab treatment provided clinically meaningful results.

This latest analysis included patients with dMMR endometrial cancer who had measurable disease at baseline and were followed for ≥ 6 months at the data cut-off (n = 71). In the study, patients received 4 doses of dostarlimab once every 3 weeks (Q3W) 500 mg dose, and then every 6 weeks (Q6W) 1000 mg until the disease progressed. The primary endpoint was the blinded independent center review of the objective response rate (ORR) and duration of response (DOR) determined according to the solid tumor efficacy evaluation standard version 1.1 (RECIST v1.1).

It is worth mentioning that the GARNET study is the largest data set to evaluate an anti-PD-1 therapy for endometrial cancer. Research data show that the ORR of dostarlimab treatment is 42% (95% CI: 31-55), and the disease control rate (DCR) is 58% (95% CI: 45-69). Overall, 13% of patients had complete remission (PR) and 30% had partial remission (PR). At the time of data cut-off, the median follow-up time was 11.2 months, and the median DOR had not been reached (1.87+ to 19.61+ months).

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

Women with advanced or recurrent endometrial cancer have limited treatment options and a poor prognosis. The results observed in the GARNET study indicate that dostarlimab has the potential to provide a new treatment option for this challenging group of female patients.

GARNET is an ongoing phase I / IIB study that is evaluating dostarlimab as a monotherapy for patients with advanced solid tumors. The IIB part of the study included 5 expanded cohorts: dMMR / microsatellite high instability (MSI-H) endometrial cancer (cohort A1), mismatch repair of normal endometrial cancer (cohort A2), and non-small cell lung cancer Cohort E), dMMR / MSI-H non-endometrial cancer (cohort F), platinum-resistant ovarian cancer without BRCA mutations (cohort G). Currently, the GARNET study is still enrolling patients.

Endometrial cancer (EC) is a major type of uterine cancer, formed in the endometrium. EC can be divided into mismatch repair defects / high microsatellite instability (dMMR / MSI-H) or normal mismatch repair / microsatellite stability (MSI-H). For patients with EC whose disease progresses during or after first-line treatment, the treatment options are limited. EC is the sixth most common female cancer in the world.

dostarlimab is a research-based humanized anti-PD-1 monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with the ligands PD-L1 and PD-L2.

In addition to the GARNET study, GlaxoSmithKline is also evaluating dostarlimab combined with standard care (chemotherapy) in women with relapsed or primary advanced endometrial cancer in the phase III RUBY trial. In addition, the company is also evaluating dostarlimab in combination with other drugs to treat patients with advanced solid tumors or metastatic cancer. (