BRIEF SUMMARY

DOSTARLIMAB- gxly- (Apr 2021)

Indn-    To treat endometrial cancer 

Comp-   Injection: 500 mg/10 mL (50 mg/mL) solution in a single-dose vial.             Dose 1 through 4: 500 mg every 3 weeks. 

ADR-

CI-  None

WARNINGS-

• Immune-mediated adverse reactions can occur in any organ system or tissue, including the following: immune-mediated pneumonitis immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis, and immune-mediateddermatologic adverse reactions.

Pat Inform-

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

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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

HIGHLIGHTS OF PRESCRIBING INFORMATION

 INDICATIONS AND USAGE

JEMPER is a programmed death receptor (PD 1) blocking antibody indicated for the 

for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced or recurrent endometrial cancer,as dretermined by an FDAapproved test that has progressed in a following prior trement with a platimum containg regimen

This indication is approved in a quick application based on time response rate and for durability of response. Continous approval of this indication may be contingent upon verification and description ot clinical beneit in a confitmatory trial

Initial U.S. Approval: 2021 

DOSAGE AND ADMINISTRATION

• Dose 1 through 4: 500 mg every 3 weeks. 

• Subsequent dosing beginning 3 weeks after Dose 4 (Dose 5 onwards): 1,000 mg every 6 weeks (

• Administer as an intravenous infusion over 30 minutes. 

DOSAGE FORMS AND STRENGTHS

Injection: 500 mg/10 mL (50 mg/mL) solution in a single-dose vial. 

CONTRAINDICATIONS

None

WARNINGS AND PRECAUTION

• Immune-mediated adverse reactions can occur in any organ system or tissue, including the following: immune-mediated pneumonitis immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis, and immune-mediateddermatologic adverse reactions.

Monitor for signs and symptoms ofimmune-mediated adverse reactions. Evaluate clinical chemistries including liver and thyroid function, at baseline and periodically during treatment. Withhold or permanently discontinue JEMPERLI and administer corticosteroids based on the severity of reaction. 

• Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue JEMPERLI based on severity of reaction. 

• Complications of allogeneic HSCT after PD-1/L-1–blocking antibody Follow patients closely for evidence of transplant-related complications and intervene promptly. 

• Embryo-fetal toxicity: Can cause fetal harm. Advise females of vreproductive potential of the potential risk to a fetus and to use effective contraception.

DOSAGE AND ADMINISTRATION

• Dose 1 through 4: 500 mg every 3 weeks. 

• Subsequent dosing beginning 3 weeks after Dose 4 (Dose 5 onwards): 1,000 mg every 6 weeks (

• Administer as an intravenous infusion over 30 minutes. 

DOSAGE FORMS AND STRENGTHS

Injection: 500 mg/10 mL (50 mg/mL) solution in a single-dose vial. 

 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.

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.

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 population-

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).

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 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.

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.