BRIEF SUMMARY

AMIVANTAMAB-vmjw- (May 2021)

Indn-    to treat adult with subset of non-small   cell cancer

Comp-   Injection: 350 mg/7 mL (50 mg/mL) solution in a single-dose vial           Administer via a peripheral line on Week 1 and Week 2.                                                   Administer RYBREVANT weekly for 4 weeks, with the initial dose as a split infusion in Week 1 on Day 1 and Day 2, then administer every 2 weeks thereafter.      

ADR-    The most common adverse reactions (= 20%) were rash, IRR, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting.

CI-   None.

WARNINGS -

 Infusion-Related Reactions (IRR):                                                                                 Interrupt infusion at the first sign of IRRs. Reduce infusion rate or permanently discontinue based on severity. 

Interstitial Lung Disease (ILD)/Pneumonitis:                                                                 Monitor for new or worsening symptoms indicative of ILD. Immediately withhold

Pat Inform-

Infusion-Related Reactions -Advise patients that  can cause infusion-related reactions, the majority of which may occur with the first infusion.  Advise patients to alert their healthcare provider immediately for any signs or symptoms of infusion-related reactions 

Interstitial Lung Disease/Pneumonitis -Advise patients of the risks of interstitial lung disease (ILD)/pneumonitis. Advise patients to immediately contact their healthcare provider for new or worsening respiratory symptoms

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U.S. FDA APPROVED DRUGS SURING 2021                                          

Serial No 21

Name of the Drug-    RYBREVANT

Active Ingredient -   Amivantamab-vmjw

Pharmacological Classification-   To treat adult with subset of non-small                                                                                cell cancer

                                                                                                                                                  Date of Approval-          5/21/2021

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use               RYBREVANT™ safely and effectively.

See full prescribing information for RYBREVANT. RYBREVANT (amivantamab-vmjw) injection, for intravenous use

Initial U.S. Approval: 2021

INDICATIONS AND USAGE-

 RYBREVANT is a bispecific EGF receptor-directed and MET receptordirected antibody indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

 This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

ADVERSE REACTIONS-                                                              

 The most common adverse reactions (= 20%) were rash, IRR, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting.

The most common Grade 3 or 4 laboratory abnormalities (= 2%) were decreased lymphocytes, decreased albumin, decreased phosphate, decreased potassium, increased alkaline phosphatase, increased glucose,

CONTRAINDICATIONS-

 None.

WARNINGS AND PRECAUTIONS-

 Infusion-Related Reactions (IRR):                                                                                 Interrupt infusion at the first sign of IRRs. Reduce infusion rate or permanently discontinue RYBREVANT based on severity. 

Interstitial Lung Disease (ILD)/Pneumonitis:                                                                 Monitor for new or worsening symptoms indicative of ILD. Immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Dermatologic Adverse Reactions:                                                                              May cause rash including acneiform dermatitis and toxic epidermal necrolysis. Withhold, dose reduce or permanently discontinue RYBREVANT based on severity.

Ocular Toxicity:                                                                                                     Promptly refer patients with worsening eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT based on severity.

 Embryo-Fetal Toxicity:                                                                                                Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception.

DOSAGE AND ADMINISTRATION-

 • The recommended dosage of RYBREVANT is based                                                      • Administer premedications as recommended.                                                                   • Administer via a peripheral line on Week 1 and Week 2.                                                  • Administer RYBREVANT weekly for 4 weeks, with the initial dose as a split infusion in Week 1 on Day 1 and Day 2, then administer every 2 weeks thereafter.                               

Administer diluted RYBREVANT intravenously according to the infusion rates            Body Weight (at Baseline) Recommended Dose Less than 80 kg 1050 mg (3 vials) Greater than or equal to 80 kg 1400 mg (4 vials)

DOSAGE FORMS AND STRENGTHS-                                                                              Injection: 350 mg/7 mL (50 mg/mL) solution in a single-dose vial 

 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Infusion-Related Reactions Advise patients that RYBREVANT can cause infusion-related reactions, the majority of which may occur with the first infusion.                      Advise patients to alert their healthcare provider immediately for any signs or symptoms of infusion-related reactions 

Interstitial Lung Disease/Pneumonitis -Advise patients of the risks of interstitial lung disease (ILD)/pneumonitis. Advise patients to immediately contact their healthcare provider for new or worsening respiratory symptoms

 Dermatologic Adverse Reactions -Advise patients of the risk of dermatologic adverse reactions.                                                                                                                            Advise patients to limit direct sun exposure, to use broad spectrum UVA/UVB sunscreen, and to wear protective clothing during treatment with RYBREVANT.                         Advise patients to apply alcohol free emollient cream to dry skin.

Ocular Toxicity- Advise patients of the risk of ocular toxicity. Advise patients to contact their ophthalmologist if they develop eye symptoms and advise discontinuation of contact lenses until symptoms are evaluated

 Paronychia -Advise patients of the risk of paronychia. Advise patients to contact their healthcare provider for signs or symptoms of paronychia

 Embryo-Fetal Toxicity -Advise females of reproductive potential of the potential risk to a fetus, to use effective contraception during treatment with RYBREVANT and for 3 months after the final dose, and to inform their healthcare provider of a known or suspected pregnancy.

Lactation- Advise women not to breastfeed during treatment with RYBREVANT and for 3 months after the final dose 

Product of Ireland Manufactured by: Janssen Biotech, Inc. Horsham, PA 19044 U.S. License Number 1864 © 2021 Janssen Pharmaceutical Companies Reference ID: 4798968

 CLINICAL PHARMACOLOGY

1.Mechanism of Action-                                                                                            Amivantamab-vmjw is a bispecific antibody that binds to the extracellular domains of EGFR and MET. In in vitro and in vivo studies amivantamab-vmjw was able to disrupt EGFR and MET signaling functions through blocking ligand binding and, in exon 20 insertion mutation models, degradation of EGFR and MET.

2. Pharmacodynamics -                                                                                                The exposure-response relationship and time-course of pharmacodynamic response of amivantamab-vmjw have not been fully characterized in patients with NSCLC with EGFR exon 20 insertion mutations.

3.Pharmacokinetics -                                                                                               Amivantamab-vmjw exposures increased proportionally over a dosage range from 350 to 1750 mg (0.25 to 1.25 times the maximum approved recommended dosage).

Steady state of amivantamab-vmjw concentrations was achieved by the 9th infusion. The accumulation ratio at steady state was

4. Distribution-                                                                                                               The amivantamab-vmjw mean (± SD) volume of distribution is 5.13 (± 1.78) L.

5.Elimination The mean (± SD) clearance of amivantamab-vmjw is 360 (± 144) mL/day and the terminal half-life is 11.3 (± 4.53) days.

6.Specific Populations -No clinically meaningful differences in the pharmacokinetics of amivantamab-vmjw were observed based on age (range: 32-87 years), sex, race, creatinine clearance (CLcr 29 to 276 mL/min), or mild hepatic impairment [(total bilirubin = ULN and AST > ULN) or (ULN < total bilirubin = 1.5 times ULN)].

The pharmacokinetics of amivantamab-vmjw have not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min) or patients with moderate (total bilirubin 1.5 to 3 times ULN) to severe (total bilirubin > 3 times ULN) hepatic impairment.

Body Weight Increases in body weight increased the volume of distribution and clearance of amivantamab-vmjw. Amivantamab-vmjw exposures are 30-40% lower in patients who weighed = 80 kg compared to patients with body weight < 80 kg at the same dose.

Exposures of amivantamab-vmjw were comparable between patients who weighed < 80 kg and received 1050 mg dose and patients who weighed = 80 kg and received 1400 mg dose.

 USE IN SPECIFIC POPULATIONS -                                                                   

1.Pregnancy Risk Summary-                                                                                    Based on the mechanism of action and findings in animal models, RYBREVANT can cause fetal harm when administered to a pregnant woman.                                                There are no available data on the use of RYBREVANT in pregnant women or animal data to assess the risk of RYBREVANT in pregnancy.

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.

RYBREVANT can cause fetal harm or developmental anomalies. In mice, EGFR is critically important in reproductive and developmental processes including blastocyst implantation, placental development, and embryo-fetal/postnatal survival and development.

2.Lactation Risk Summary -                                                                                       There are no data on the presence of amivantamab-vmjw in human milk on milk production, or its effects on the breastfed child.

Because of the potential for serious adverse reactions from RYBREVANT in breast-fed infants, advise women not to breast-feed during treatment with RYBREVANT and for 3 months after the final dose.

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

Pregnancy Testing -                                                                                                             Verify pregnancy status of females of reproductive potential prior to initiating RYBREVANT.

Contraception Females-                                                                                                   Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the final dose of RYBREVANT.

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

5.Geriatric Use -                                                                                                               Of the 129 patients treated with RYBREVANT, 41% were 65 years of age or older, and 9% were 75 years of age or older. No clinically important differences in safety or efficacy were observed between patients who were =65 years of age and younger patients.