Abstract

REVIEW OF DOSTARLIMAB: A BREAKTHROUGH IN IMMUNO ONCOLOGY

Vaishnavi R. Gaikwad*, Prof. Babasaheb L. Chopade and Dr. Megha T. Salve

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Abstract

Overview of Dostarlimab and Immunotherapy in Cancer Treatment Immunotherapy has emerged as a transformative pillar in cancer treatment, focusing on reinvigorating the immune system to fight malignancies. Various immunotherapies, notably immune checkpoint inhibitors (ICIs), monoclonal antibodies, and chimeric antigen T-cell therapy, have shown promising efficacy by targeting immune checkpoints, including CTLA-4 and PD-1 proteins, thereby enhancing immune responses against cancer cells. Dostarlimab, a humanized IgG4 monoclonal antibody developed by GlaxoSmithKline, is a recent addition to the monoclonal antibody class. By binding to PD-1 on T cells, it prevents interactions with PD-L1 and PD-L2 on cancer cells, restoring the immune system’s anti-tumor function. This drug received FDA approval for treating mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer following platinum-based chemotherapy and has demonstrated efficacy in treating various solid tumors. The mechanism of dostarlimab centers on immune checkpoint inhibition, where it blocks the PD- 1/PD-L1 pathway, reversing immune suppression in cancers where PD-L1 is overexpressed. Pharmacodynamic studies show its high affinity for PD-1 in humans and primates, enhancing IL-2 production in immune assays and demonstrating a synergistic effect with LAG3 or TIM3 antibodies. Pharmacokinetic studies report dose-dependent increases in exposure metrics, confirming its effectiveness across varied doses. Clinical applications of dostarlimab extend to endometrial and rectal cancers, where it has shown efficacy in GARNET trials. Its safety profile aligns with other ICIs, reporting treatment-emergent adverse events such as fatigue, nausea, and immune-related adverse effects in a minority of cases. In trials, serious adverse events led to treatment discontinuation in a small percentage of patients, underscoring the need for vigilant management of side effects. Ongoing clinical trials, including studies in NSCLC, continue to validate its role in the oncology landscape, with promising data supporting the integration of dostarlimab in immunotherapeutic regimens across cancer types.

Keywords: Immunotherapy, Cancer treatment, Dostarlimab, PD-1/PD-L1 pathway, Immune checkpoint inhibitors (ICIs), Monoclonal antibody.