The Food and Drug Administration (FDA) has granted accelerated approval to dostarlimab-gxly (Jemperli) for the treatment of adults with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer and solid tumors. To treat endometrial cancer, the cancer must have progressed or recurred after prior treatment with a platinum-containing regimen. To treat solid tumors, the tumors must have progressed or recurred after prior treatment and no satisfactory alternative treatment options exist. For both uses, a specific FDA-approved test must be used to make the diagnosis.

Dostarlimab-gxly is a programmed death receptor-1 (PD-1)-blocking IgG4 humanized monoclonal antibody. Blocking PD-1 receptors on T cells inhibits T-cell proliferation and cytokine production, leading to decreased tumor growth.

Dostarlimab-gxly's efficacy was determined in a nonrandomized, multicenter, open-label, multicohort trial of 71 patients with dMMR endometrial cancer and 209 patients with dMMR solid tumors. The overall response rate in those with endometrial cancer was 42.3%, with 93.3% having a duration of response of at least six months. For those with solid tumors, the overall response rate was 41.6%, with 95.4% having a duration of response of six months or more. The overall response rate and duration of response were used as surrogate end points in the prediction of potential clinical benefit leading to accelerated approval.

Labeled warnings and precautions for dostarlimab-gxly include immune-mediated adverse effects, which can be severe or fatal and occur in any organ system or tissue, such as immune-mediated pneumonitis, colitis, hepatitis, or nephritis. The label also warns of infusion-related reactions, complications of allogenic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

Common adverse effects were similar in patients with dMMR endometrial cancer and solid tumors and included fatigue/asthenia, anemia, diarrhea, and nausea. The most common serious laboratory abnormalities were decreased lymphocytes, sodium, or albumin and increased alkaline phosphatase. For those with dMMR endometrial cancer, an additional common adverse effect was constipation, and changes in laboratory values also included anemia, decreased leukocytes, and elevated alanine aminotransferase and creatinine.

Dostarlimab-gxly is administered as an IV infusion over 30 minutes using a designated line. If the infusion-related reaction is severe, the drug may need to be withheld or discontinued permanently. Due to the risk of fetal toxicity, women of reproductive age should use effective contraception during treatment and for four months after the last dose.

For complete prescribing information for dostarlimab-gxly, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761223s000lbl.pdf.