FDA Grants Accelerated Approval to Dostarlimab for Solid Tumors

The FDA granted an accelerated approval to dostarlimab-gxly (Jemperli), a programmed cell death receptor-1 (PD-1) blocking antibody, for the treatment of adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors that have progressed on or following prior treatment and who have no satisfactory alternative treatment options, according to a press release by GlaxoSmithKline (GSK).¹ 

Dostarlimab-gxly works by blocking interaction with PD-L1 and PD-L2 ligands. It is being studied as both a monotherapy and in combination with advanced endometrial cancer, epithelial ovarian cancer, and advanced solid tumors. 

“For patients with tumors expressing the dMMR biomarker, there continues to be a significant need for new and effective treatments. I’m excited about GSK’s second oncology FDA approval this year, and the new treatment option it provides for these patients,” said Hal Barron, MD, chief scientific officer and president of research and development at GSK, in a press release.

Approval is based on results of the GARNET trial (NCT02715284).² The phase 1 non-randomized trial had an actual enrollment of 740 participants and an estimated completion date of April 2024. Primary end points of part 1 and 2 include the number of treatment-emergent adverse events (TEAEs), overall response rate (ORR), and duration of response. Secondary end points include immune-related ORR, progression-free survival (PFS), and disease control rate.

During the study, patients received 500 mg of the agent intravenously once every 3 weeks for 4 doses followed by 1000 mg once every 6 weeks or until disease progression or unacceptable toxicity.

The ORR in all dMMR solid tumors was 41.6% with a complete response of 9.1% and a partial response rate of 32.5%. The median duration of response was 34.7 months with 95.4% of patients maintaining the response for at least 6 months. For patients in the dMMR solid tumor non-endometrial cancer cohort, the ORR was 38.7%.

In total, 267 patients with recurrent or advanced dMMR solid tumors were evaluated for safety. The most common reported AEs were fatigue/asthenia (42%), anemia (30%), diarrhea (25%) and nausea (22%). Common grade 3 or 4 adverse reactions (≥2%) were anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury. Reported grade 3 or 4 laboratory abnormalities (≥2%) included decreased lymphocytes, decreased sodium, increased alkaline phosphatase and decreased albumin.

“Dostarlimab is an important new treatment option for patients with mismatch repair-deficient recurrent or advanced solid cancers who have progressed and have no alternative options. As we saw in the GARNET trial, of those patients who respond to treatment with dostarlimab, nearly all continued to respond for six months or longer,” said Jubilee Brown, MD, professor and division director of Gynecologic Oncology at Atrium Health Levine Cancer Institute, and investigator on the GARNET study in the release.

_REFERENCES:

_{1. GSK receives FDA accelerated approval for JEMPERLI (dostarlimab-gxly) for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumours. News release. GlaxoSmithKline. August 17, 2021. Accessed August 17, 2021. https://bit.ly/3yVK8Up.}

_{2. Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors (GARNET). ClincialTrials.gov. Accessed August 17, 2021. https://bit.ly/2W1WuMF.}