Dostarlimab (Jemperli): A Comprehensive Clinical and Scientific Monograph

1.0 Executive Summary

Dostarlimab, marketed under the brand name Jemperli, is a humanized immunoglobulin G4 (IgG4) monoclonal antibody that has emerged as a pivotal therapeutic agent in the field of immuno-oncology. As a programmed death receptor-1 (PD-1) blocking antibody, dostarlimab functions by reinvigorating the host's immune system to combat malignant cells. Its mechanism hinges on high-affinity binding to the PD-1 receptor on T-cells, thereby preventing its interaction with ligands PD-L1 and PD-L2 and releasing the "brake" on anti-tumor immunity.

The clinical development of dostarlimab has been marked by rapid and significant success, particularly in cancers characterized by a deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) biomarker status. Landmark clinical trials have established dostarlimab as a new standard of care in endometrial cancer (EC). The GARNET study demonstrated robust and exceptionally durable responses for dostarlimab monotherapy in patients with previously treated, advanced dMMR EC. Subsequently, the RUBY trial established its role in the first-line setting, where its addition to chemotherapy conferred a profound survival benefit in patients with dMMR/MSI-H primary advanced or recurrent EC and also improved overall survival in the broader all-comer population, leading to expanded global approvals.

Beyond endometrial cancer, dostarlimab has produced unprecedented results in a phase II study for locally advanced dMMR rectal cancer, achieving a 100% clinical complete response rate and heralding a potential paradigm shift toward non-operative, curative-intent management. This has been complemented by a tumor-agnostic accelerated approval for the treatment of any dMMR solid tumor that has progressed on prior therapy.