JEMPERLI is a programmed death receptor-1 (PD-1)–blocking antibody

U.S. FDA APPROVED DRUGS SURING 2021                                          

Serial No 17

Name of the Drug-    JEMPERLI

Active Ingredient -   Dostarlimab-gxly

Pharmacological Classification-   To treat endometrial cancer

                                                                                                                                                    Date of Approval-          4/22/2021

INDICATIONS AND USAGE-                                                                               

JEMPERLI is a prorammed death rececetor (PD 1) blocking antibody indicated for thetreatment of adults patients with mismatch replacement deficient (dMMR) recurrent or advanced endometrial cancer as determined by an FDA Approved test that has progressesd on or following prior treament with a plantimum containg regimen

This indication is approved in a accelrated application based time response rate   and durability response . Coniinued approval of this indication may be contignent upon verification and description on clinical benefit in a confirmatory trial(s)

This indication is approved under accelerated approval based on tumor response rate and durability of response [see Clinical Studies (

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

 Recommended Dosage-                                                                                              The recommended dosage of JEMPERLI is:                                                                       • Dose 1 through Dose 4: 500 mg every 3 weeks

• Subsequent dosing beginning 3 weeks after Dose 4 (Dose 5 onwards): 1,000 mg every 6 weeks Administer JEMPERLI as an intravenous infusion over 30 minutes. Treat patients until disease progression or unacceptable toxicity.

DOSAGE FORMS AND STRENGTHS-                                                                  Injection: 500 mg/10 mL (50 mg/mL) clear to slightly opalescent, colorless to yellow solution in a single-dose vial for intravenous infusion after dilution.

CONTRAINDICATIONS

None.

 WARNINGS AND PRECAUTIONS

1 Immune-Mediated Adverse Reactions- JEMPERLI is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance, and inducing immune-mediated adverse reactions. 

2.Immune-Mediated Pneumonitis- JEMPERLI can cause immune-mediated pneumonitis, which can be fatal. The incidence of pneumonitis in patients receiving PD-1/PD-L1 inhibitors, including JEMPERLI, may be increased in patients who have received prior thoracic radiation.

3.Immune-Meedicateated Colitis -JEMPERLI can cause immune-mediated colitis. Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies.

In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.4% (6/444) of patients receiving JEMPERLI, including Grade 3 (0.7%) and Grade 2 (0.7%) adverse reactions.

4.Immune-Mediated Hepatitis- JEMPERLI can cause immune-mediated hepatitis, which can be fatal. Immune-mediated hepatitis occurred in 0.2% (1/444) of patients receiving JEMPERLI, which was Grade 3. Systemic corticosteroids were required and the event resolved.

5.Immune-Mediated Endocrinopathies- Adrenal Insufficiency: JEMPERLI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated.

Withhold JEMPERLI if not clinically stable 

 Recommended Dosage-                                                                                               

  The recommended dosage of JEMPERLI is:                                                                       • Dose 1 through Dose 4: 500 mg every 3 weeks

• Subsequent dosing beginning 3 weeks after Dose 4 (Dose 5 onwards): 1,000 mg every 6 weeks Administer JEMPERLI as an intravenous infusion over 30 minutes. Treat patients until disease progression or unacceptable toxicity.

DOSAGE FORMS AND STRENGTHS-                                                                  Injection: 500 mg/10 mL (50 mg/mL) clear to slightly opalescent, colorless to yellow solution in a single-dose vial for intravenous infusion after dilution.

 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Immune-Mediated Adverse Reactions-                                                                            Inform patients of the risk of immune-mediated adverse reactions that may be severe or fatal, may occur after discontinuation of treatment, and may require corticosteroid or other treatment and interruption or discontinuation of JEMPERLI. These reactions may include:

• Pneumonitis: Advise patients to contact their healthcare provider immediately for new or worsening cough, chest pain, or shortness of breath

• Colitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain

• Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, or easy bruising or bleeding

• Immune-mediated endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of hypothyroidism, hyperthyroidism, thyroiditis, adrenal insufficiency, hypophysitis, or type 1 diabetes mellitus

• Nephritis: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis

• Severe skin reactions: Advise patients to contact their healthcare provider immediately for any signs or symptoms of severe skin reactions, SJS, or TEN

• Other immune-mediated adverse reactions:

• Advise patients that immune-mediated adverse reactions can occur and may involve any organ system, and to contact their healthcare provider immediately for any new signs or symptoms

Infusion-Related Reactions-

• Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions

Embryo-Fetal Toxicity • Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy

Use in Specific Populations. • Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after the last dose.

Lactation • Advise women not to breastfeed during treatment with JEMPERLI and for 4 months after the last dose 

Trademarks are owned by or licensed to the GSK group of companies. Manufactured by GlaxoSmithKline LLC Philadelphia, PA 19112 U.S. License No. 1727

 CLINICAL PHARMACOLOGY -                                                                     

1. Mechanism of Action-                                                                                               Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors

2. Pharmacodynamics-                                                                                        Dostarlimab-gxly exposure-response relationships have not been fully characterized.

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.

3. Pharmacokinetics-                                                                                                    The pharmacokinetics of dostarlimab-gxly were evaluated in patients with various solid tumors, including 150 patients with EC. Mean Cmax, AUC0-inf, and AUC0-tau increased proportionally over the dose range of 1.0 to 10 mg/kg.

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.

Specific Populations-                                                                                                     No clinically significant differences in the pharmacokinetics of dostarlimab-gxly were observed based on age (24 to 86 years), sex (79% female), race/ethnicity (78% White, 2% Asian, 4% African American, and 16% other), tumor types, and renal impairment based on the estimated creatinine clearance (CLCR mL/min) (normal: CLCR =90 mL/min, n = 173; mild: CLCR = 60-89 mL/min, n = 210; moderate: CLCR = 30-59 mL/min, n = 90; severe: CLCR = 15-29 mL/min, n = 3; and end-stage renal disease: CLCR <15 mL/min, n = 1) and hepatic impairment as measured by total bilirubin (TB) and aspartate aminotransferase (AST) (normal: TB and AST less than or equal to upper limit of normal [ULN], n = 425; mild: TB>ULN to 1.5 ULN or AST>ULN, n = 48; and moderate: TB>1.5-3 ULN, any AST, n = 4).

USE IN SPECIFIC POPULATIONS

1 Pregnancy Risk Summary-

Based on its mechanism of action, JEMPERLI can cause fetal harm when administered to a pregnant woman 

There are no available data on the use of JEMPERLI in pregnant women.

Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death (see Data).

Human IgG4 immunoglobulins (IgG4) are known to cross the placental barrier; therefore, dostarlimab-gxly has the potential to be transmitted from the mother to the developing fetus.

Advise women of the potential risk to a fetus

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively..

2. Lactation Risk Summary-

 There is no information regarding the presence of dostarlimab-gxly in human milk or its effects on the breastfed child or on milk production.

Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 4 months after the last dose of JEMPERLI

3. Females and Males of Reproductive Potential-                                                  JEMPERLI can cause fetal harm when administered to a pregnant woman  

Pregnancy Testing- Verify pregnancy status in females of reproductive potential prior to initiating JEMPERLI 

Contraception Females: Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after the last dose.

4. Pediatric Use -The safety and efficacy of JEMPERLI have not been established in pediatric patients.

5. Geriatric Use- Of the 444 patients treated with JEMPERLI, 49% were younger than 65 years, 39% were aged 65 through 75 years, and 12% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.