JEMPERLI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for JEMPERLI (JEMPERLI).
JEMPERLI (dostarlimab-gxly) is a humanized monoclonal antibody that binds to the programmed death receptor-1 (PD-1) and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.
| Metabolism | Metabolism of dostarlimab-gxly is expected to be via catabolic pathways into small peptides and amino acids. No major metabolic enzymes are involved. |
| Excretion | Metabolism is not fully characterized; as a monoclonal antibody, it is expected to be degraded into small peptides and amino acids via catabolic pathways. No renal or biliary excretion of intact drug. Less than 1% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 27.4 days (range 12.5–47.1 days) in patients with recurrent or advanced endometrial cancer. This long half-life supports a 6-week dosing interval. |
| Protein binding | Dostarlimab (JEMPERLI) is a monoclonal antibody; no specific protein binding data. Typically, mAbs have negligible binding to plasma proteins other than target antigen. |
| Volume of Distribution | Volume of distribution (Vd) at steady state approximately 7.8 L (range 5.4–11.0 L). This low Vd (approx. 0.1 L/kg) is consistent with limited distribution to tissues, primarily in vascular space. |
| Bioavailability | Administered as intravenous infusion; bioavailability is 100% by IV route. No oral formulation available. |
| Onset of Action | Time to clinical response (partial or complete) varies; median time to response was 3.6 months (range 0.9–27.5 months) in clinical trials. No immediate effect; requires multiple doses for antitumor activity. |
| Duration of Action | Duration of response (DOR) median 26.6 months (95% CI: 20.2–not reached) in endometrial cancer. Treatment continues until disease progression or unacceptable toxicity. |
500 mg intravenously every 3 weeks for 4 doses, then 1000 mg intravenously every 6 weeks until disease progression or unacceptable toxicity.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment (CrCl >= 30 mL/min). Not studied in severe renal impairment (CrCl < 30 mL/min). |
| Liver impairment | No dose adjustment recommended for mild hepatic impairment (Child-Pugh A). Not studied in moderate or severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. No recommended dose. |
| Geriatric use | No specific dose adjustment recommended based on age. Elderly patients may have higher incidence of adverse reactions; monitor closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for JEMPERLI (JEMPERLI).
| Breastfeeding | There are no data on the presence of dostarlimab in human milk, effects on the breastfed child, or effects on milk production. Human IgG is present in human milk, but published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for at least 4 months after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | Based on its mechanism of action (programmed cell death protein 1 [PD-1] blockade), JEMPERLI (dostarlimab) is expected to cause fetal harm when administered to a pregnant woman. Human IgG immunoglobulins are known to cross the placental barrier; therefore, dostarlimab may be transmitted from the mother to the developing fetus. In animal studies, PD-1/PD-L1 pathway blockade has been associated with increased risk of immune-mediated rejection of the developing fetus, leading to fetal death. No adequate and well-controlled studies exist in pregnant women. Advise women of the potential risk to the fetus. Use effective contraception during treatment and for at least 4 months after the last dose. |
■ FDA Black Box Warning
Immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and severe skin reactions, can occur. Withhold or permanently discontinue based on severity.
| Serious Effects |
None.
| Precautions | ["Immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies (e.g., hypothyroidism, hyperthyroidism, adrenal insufficiency), nephritis, and severe skin reactions.","Infusion-related reactions.","Embryo-fetal toxicity."] |
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| Fetal Monitoring | Monitor for signs and symptoms of immune-mediated adverse reactions, including but not limited to pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic reactions. In pregnant women, additional monitoring for fetal well-being (e.g., ultrasound for fetal growth and amniotic fluid volume) is recommended. If dostarlimab is used during pregnancy, or if the patient becomes pregnant while taking the drug, apprise the patient of the potential hazard to the fetus. |
| Fertility Effects | Based on animal studies, JEMPERLI may impair fertility in females. In a 3-month repeat-dose toxicity study in cynomolgus monkeys administered dostarlimab, there were no notable effects on the male reproductive organs; however, female reproductive organs were not evaluated. The effect on human fertility is unknown. |