FDA News: Issue 11, May 2021

Author: [AUTHOR] Published on 5/14/2021 8:03:00 AM

FDA Approves JEMPERLI (Dostarlimab-gxly) for Adult Patients with Mismatch Repair Deficient Recurrent or Advanced Endometrial Cancer

On April 22, 2021, the US Food and Drug Administration (FDA) approved JEMPERLI (dostarlimab-gxly) for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer (EC), as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Select patients with recurrent or advanced EC that has progressed on or following prior treatment with a platinum-containing regimen for treatment with JEMPERLI based on the presence of dMMR in tumor specimens. Information on FDA-approved tests for the detection of dMMR status is available at http://www.fda.gov/CompanionDiagnostics.

The approved recommended dosage of JEMPERLI is 500 mg every 3 weeks for Dose 1 through Dose 4, and then 1,000 mg every 6 weeks for Dose 5 onwards (beginning 3 weeks after Dose 4). Administer JEMPERLI as an intravenous infusion over 30 minutes. Treat patients until disease progression or unacceptable toxicity.

Additional information regarding dosage and administration as well as warnings and precautions about immune-mediated adverse reactions in various organ systems and tissues that can be severe or fatal, infusion-related reactions, complications of allogenic HSCT after PD-1/PD-L1-blocking antibody, and embryo-fetal toxicity can be found in the full prescribing information linked below.

Mechanism of Action (MOA), Pharmacokinetics (PK), and Pharmacodynamics (PD)
  • MOA: Dostarlimab-gxly is a programmed death receptor-1 (PD-1)–blocking antibody.
  • General PK: Mean Cmax, AUC0-inf, and AUC0-tau increased proportionally over the dose range of 1 to 10 mg/kg. The Cycle 1 mean (%CV) Cmax and AUC0-tau of dostarlimab-gxly are 171 mcg/mL (20%) and 35,730 mcg*h/mL (20%) at the dose of 500 mg once every 3 weeks and 309 mcg/mL (31%) and 95,820 mcg*h/mL (29%) at the dose of 1,000 mg every 6 weeks, respectively.
  • Distribution: The mean (%CV) volume of distribution of dostarlimab-gxly at steady state is 5.3 L (12%).
  • Elimination: The mean terminal elimination half-life of dostarlimab-gxly is 25.4 days and its mean (%CV) clearance is 0.007 L/h (31%) at steady state.
  • Metabolism: Dostarlimab-gxly is expected to be metabolized into small peptides and amino acids by catabolic pathways.
  • PD: Dostarlimab-gxly provides sustained target engagement as measured by PD-1 binding and stimulation of IL-2 production throughout the dosing interval at the recommended dose.
  • Immunogenicity: Because of the small number of patients who developed anti-drug antibodies during treatment, the impact of immunogenicity on the efficacy and safety of dostarlimab-gxly is inconclusive.
Use in Specific Populations
No clinically significant differences in the pharmacokinetics of dostarlimab-gxly were observed based on age (24 to 86 years), sex, race/ethnicity (White, Asian, African American), tumor types, renal impairment, end-stage renal disease, or hepatic impairment.

Efficacy and Safety
The efficacy of JEMPERLI was evaluated in a multicenter, multicohort, open-label study conducted in patients with advanced solid tumors, consisting of a cohort of patients with dMMR recurrent or advanced EC who had progressed on or after treatment with a platinum-containing regimen. Additional information regarding the efficacy trial can be found in the full prescribing information linked below.

Most common adverse reactions (≥ 20%) are fatigue/asthenia, nausea, diarrhea, anemia, and constipation.

Full prescribing information is available at https://go.usa.gov/xH7yQ.

Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products, which are often available shortly following approval. 

A non-comprehensive list of examples of clinical substrates, inhibitors and inducers for metabolic and transporter system related interactions may be found at https://go.usa.gov/xXY9C.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA's MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178), or by mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

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We always welcome your thoughts regarding the format, content, and utility of this communication. Comments may be sent via email to ocp@fda.hhs.gov.

This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.

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