Dostarlimab, sold under the brand name Jemperli, is a monoclonal antibody used as a medication for the treatment of endometrial cancer. Dostarlimab is a programmed death receptor-1 (PD-1)–blocking monoclonal antibody.
Endometrial cancer (EC) is a disease where cancerous cells reside in the lining of the uterus (endometrium). There are four stages in EC, ranging from staying settled in the endometrium to the cancer spreading to other organs in the body. This disease can be treated if discovered at the beginning of development.In those with chemoresistant MSI-high tumors, studies conducted on dostarlimab and pembrolizumab display promising results of the tumors reacting well to the therapies.
Inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the treatment landscape for patients with cancer. Clinical activity of anti-PD-(L)1 antibodies has resulted in increased median overall survival and durable responses in patients across selected tumor types. To date, 6 PD-1 and PD-L1, here collectively referred to as PD-(L)1, pathway inhibitors are approved by the US Food and Drug Administration for clinical use. The availability of multiple anti-PD-(L)1 antibodies provides treatment and dosing regimen choice for patients with cancer. Here, we describe the nonclinical characterization of dostarlimab (TSR-042), a humanized anti-PD-1 antibody, which binds with high affinity to human PD-1 and effectively inhibits its interaction with its ligands, PD-L1 and PD-L2. Dostarlimab enhanced effector T-cell functions, including cytokine production, in vitro. Since dostarlimab does not bind mouse PD-1, its single-agent antitumor activity was evaluated using humanized mouse models. In this model system, dostarlimab demonstrated antitumor activity as assessed by tumor growth inhibition, which was associated with increased infiltration of immune cells. Single-dose and 4-week repeat-dose toxicology studies in cynomolgus monkeys indicated that dostarlimab was well tolerated. In a clinical setting, based on data from the GARNET trial, dostarlimab (Jemperli) was approved for the treatment of adult patients with mismatch repair-deficient recurrent or advanced endometrial cancer that had progressed on or following prior treatment with a platinum-containing regimen. Taken together, these data demonstrate that dostarlimab is a potent anti-PD-1 receptor antagonist, with properties that support its continued clinical investigation in patients with cancer.
Dostarlimab, developed by Tesaro and sold to GlaxoSmithKline, is a monoclonal antibody used to target cancer.
Dostarlimab is a programmed death receptor-1 (PD-1) blocking antibody that works by targeting the PD-1/PD-L1 cellular pathway resulting in the inhibition of T-cell proliferation and cytokine production. The accelerated approval was based on data from the multicenter, multicohort, open-label phase 1 GARNET trial (ClinicalTrials.gov: NCT02715284) that evaluated dostarlimab in 71 adults with dMMR recurrent or advanced endometrial cancer who progressed on or after a platinum-containing regimen.
Patients received dostarlimab 500mg intravenously (IV) every 3 weeks for 4 doses followed by 1000mg IV every 6 weeks until disease progression or unacceptable toxicity. The major efficacy endpoints were overall response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review (BICR) according to RECIST v1.1.
Findings showed an ORR of 42.3% (95% CI, 30.6-54.6), with 12.7% of patients achieving complete response and 29.6% having partial response. The median DOR was not reached with 93.3% of patients having a response lasting at least 6 months (range: 2.6-22.4+).
As for safety, the most common adverse reactions (³20%) were fatigue/asthenia, nausea, diarrhea, anemia, and constipation. The most common grade 3 or 4 adverse reactions (³2%) were anemia and increased transaminases. Serious adverse reactions that occurred in greater than 2% of patients included sepsis, acute kidney injury, urinary tract infection, abdominal pain, and pyrexia.