Jemperli

Dostarlimab-gxly (Jemperli) is a monoclonal antibody that works by targeting the programmed death-1 receptor (PD-1), which is involved in T-cell immune surveillance of tumors. Binding of the PD-1 receptor results in blockade of the PD-1 and PD-2 ligands which generates an anti-tumor immune response and decreased tumor growth. Mismatch repair deficient (dMMR) tumors are expressed in various cancers and have high mutation rates due to the inability to repair DNA replication errors. These tumors have higher levels of neoantigens and have been found to be responsive to PD-1 targeted immunotherapy. Dostarlimab is a PD-1 inhibitor FDA-approved for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer (EC), that has progressed on or following prior treatment with a platinum-containing regimen, and are not candidates for curative surgery or radiation. It is also approved for recurrent or advanced mismatch repair deficient solid tumors that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. Continued approval of use for dMMR solid tumors is contingent upon verification of clinical benefit in confirmatory trials. It was also FDA approved for use in combination with carboplatin and paclitaxel followed by use as a single agent for primary advanced or recurrent endometrial cancer. The efficacy of dostarlimab was assessed in an open-label study in 71 patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer who had progressed on or after treatment with a platinum-containing regimen. Half of the patients had received treatment for metastatic disease and 90% had previously undergone surgery. All patients previously received a platinum-containing regimen and 40% had received 2 lines or more of treatment. Patients were excluded if they had previously received immune checkpoint inhibitor therapy. The overall response rate (ORR) with dostarlimab was 42% (95% CI 30.6, 54.6). The ORR consisted of 13% of patients with a complete response and 30% with a partial response at a median follow up of 11.2 months. The median progression-free survival was 8.1 months and the median overall survival was not reached. The most frequently reported adverse effects were asthenia, diarrhea, fatigue, nausea, anemia, and constipation. Dose interruption occurred in 23% of patients as a result of anemia, diarrhea, increased lipase, or pyrexia. Dostarlimab was permanently discontinued in 5% of patients due to elevated transaminases, sepsis, bronchitis, and pneumonitis. The National Comprehensive Cancer Network (NCCN) Guidelines provide recommendations for the use of dostarlimab for the treatment of various types of cancer. <a id="