GSK's Anti-PD-1 Therapy Dostarlimab Demonstrates Strong Efficacy in dMMR Solid Tumors with ORR of 36–43%

January 16, 2021 /BioValleyBIOON/ --GlaxoSmithKline(GSK) recently announced the latest data from Cohort F of the GARNET study on the anti-PD-1 therapy dostarlimab (formerly TSR-042) at the 2021 ASCO Gastrointestinal Cancers Symposium (ASCO GI). This cohort evaluated the efficacy and safety of dostarlimab in treating mismatch repair-deficient (dMMR) advanced non-endometrial solid tumors. The results showed that,The objective response rate (ORR) for dostarlimab treatment was 38.7%.(N=106, 95% CI: 29.4-48.6). Furthermore, after a median follow-up of 12.4 months, the median duration of response (DOR) had not been reached across various typesTumorachieved durable remission.

It should be noted that patients enrolled in Cohort F of the GARNET study had dMMR solid tumors that progressed after standard therapy, with few treatment options available. These data suggest that dostarlimab has the potential to become an important new treatment option, providing durable responses for these patients.

Dostarlimab is an investigational 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. Currently, dostarlimab is under review in the United StatesFDAand the EMA review, for the treatment of patients with recurrent or advanced dMMR/microsatellite instability-high (MSI-H) endometrial cancer who have progressed during or after platinum-based chemotherapy.

Data from the GARNET study show that,The ORR of dostarlimab in the treatment of dMMR/MSI-H endometrial cancer is 42%.(95% CI: 31–55); the disease control rate (DCR) was 58% (95% CI: 45–69). Overall, 13% of patients achieved a complete response (CR), and 30% achieved a partial response (PR). At the data cutoff, the median follow-up time was 11.2 months, and the median duration of response (DOR) had not been reached (range: 1.87+ to 19.61+ months).

GSK Senior Vice President andTumorDr. Axel Hoos, Head of R&D, stated, “We are committed to finding new ways to improve outcomes for patients with refractory cancers who have limited treatment options. These latest results from the ongoing GARNET study indicate that dostarlimab has the potential to help a broad range of patients with solid tumors harboring DNA mismatch repair deficiency.”

Image source: GSK

The GARNET study enrolled patients with dMMR non-endometrial solid tumors, the majority of whom had gastrointestinal cancers (colorectal cancer, gastric cancer, and small bowelTumor). Among these patients, the majority (n=81) had received two or more prior systemic therapies. In the study, patients received dostarlimab at a dose of 500 mg every 3 weeks for four doses, followed by 1000 mg every 6 weeks until disease progression, discontinuation, or for up to 2 years. The primary objective of the study was to assess the objective response rate (ORR) and duration of response (DoR) according to RECIST v1.1, as evaluated by blinded independent central review.

The results showed that colorectal cancer patients (n=69) and non-colorectal cancer patients (n=37, including small intestine, gastric, pancreatic, ovarian cancers,Liver Cancerconsistent with the ORR in other types of solid tumors). InIn patients with colorectal cancer, the ORR was 36.2%.(95% CI; 25.0–48.7); atIn patients without colorectal cancer, the ORR was 43.2%.(95% CI; 27.1–60.5). In Cohort F, 8% of patients achieved complete response.

Among patients who received one or more doses of dostarlimab and were evaluable for safety (n=144), dostarlimab was well tolerated, with a low discontinuation rate due to treatment-related adverse events (TRAEs) (3.5%). The most common TRAEs were asthenia (13%), diarrhea (13%), pruritus (13%), arthralgia (9%), and fatigue (9%). Grade 3 or higher TRAEs occurred in 8% of patients. No deaths related to dostarlimab were reported in the study.(Bio Valley Bioon.com)

Original Source: GSK Presents Positive Efficacy Data of Dostarlimab in Mismatch Repair-Deficient (dMMR) Solid Cancers at ASCO Gastrointestinal Cancers Symposium