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Dostarlimab is an anti-PD-1 monoclonal antibody used in the treatment of mismatch repair deficient endometrial cancers and solid tumours with no alternative treatment options.
Dostarlimab is an anti-PD-1 monoclonal antibody used in the treatment of mismatch repair deficient endometrial cancers and solid tumours with no alternative treatment options.
Approximately 13-30% of recurrent endometrial cancers involve microsatellite instability (MSI) or mismatch repair deficiency (dMMR). The mutations resulting in dMMR endometrial cancers are primarily somatic in nature (~90%), although 5-10% of cases involve germline mutations. Cancers that have mutations resulting in dMMR can upregulate the expression of programmed death receptor-1 (PD-1) ligands 1 and 2 (PD-L1 and -L2) - PD-1 is found on T-cells and, when activated, inhibits their proliferation and the production of cytokines. The binding of these ligands to PD-1 thereby functions as an immune checkpoint that downregulates the anti-tumor immune response. Dostarlimab is a monoclonal antibody targeted against PD-1 - it binds to the receptor and prevents interactions with PD-L1 and PD-L2, thus allowing the anti-tumor immune response to proceed unimpeded.
Dostarlimab-gxly is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer that has progressed despite ongoing or prior treatment with a platinum-containing chemotherapy regimen. It is also indicated for the treatment of solid tumours in adults, as determined by an FDA-approved test, that have progressed on or following prior treatment and in patients who have no satisfactory alternative treatment options. This indication is approved under accelerated approval, and continued approval for this indication may be contingent upon verification and description of and description of clinical benefit in confirmatory trials.
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