Amivantamab-vmjw (Monograph)

Brand name: Rybrevant
Drug class: Antineoplastic Agents
Molecular formula: C₆₄₇₂H₁₀₀₁₄N₁₇₃₀O₂₀₂₃S₄₆
CAS number: 2171511-58-1

Medically reviewed by Drugs.com on Feb 1, 2023. Written by ASHP.

Introduction

Antineoplastic agent; bispecific antibody directed against epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) receptor.

Uses for Amivantamab-vmjw

Non-small Cell Lung Cancer

Treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

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

Amivantamab-vmjw Dosage and Administration

General

Pretreatment Screening

Select patients for treatment based on the presence of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in tumor or plasma specimens. If no mutation is detected in a plasma specimen, test tumor tissue.
Verify pregnancy status in females of reproductive potential prior to initiating therapy.

Patient Monitoring

Monitor for signs and symptoms of infusion reactions. Infuse in settings with cardiopulmonary resuscitation medication and equipment.
Monitor for new or worsening symptoms of interstitial lung disease or pneumonitis including dyspnea, cough, and fever.

Premedication and Prophylaxis

Premedicate before administration to reduce the risk of infusion-related reactions (see Table 1).
Premedicate with an antihistamine and antipyretic before every infusion. Administer glucocorticoids before the first 2 doses (Week 1, Days 1 and 2) and as needed for subsequent doses.

Glucocorticoids are required with the initial dose (Days 1 and 2 of Week 1) and can be used as needed for subsequent doses.

Table 1. Premedication Requirements to Reduce Infusion-related Reactions.1
Medication	Dose	Route and Timing of Administration
Antihistamine	Diphenhydramine (25 to 50 mg) or equivalent	Administer IV 15–30 minutes prior to administration of amivantamab or orally 30–60 minutes prior to administration of amivantamab
Antipyretic	Acetaminophen (650 to 1000 mg)	Administer IV 15–30 minutes prior to administration of amivantamab or orally 30–60 minutes prior to administration of amivantamab
Glucocorticoid	Dexamethasone (10 mg) or methylprednisolone (40 mg) or equivalent	Administer IV 45–60 minutes prior to administration of amivantamab

Administration

IV Administration

Administer as an IV infusion after dilution. Administer IV infusion once weekly for 4 weeks, then once every 2 weeks starting at Week 5. Administer the initial dose (Week 1) as a split infusion on Days 1 and 2 as described in Table 2 and 3.

During Weeks 1 and 2, infuse via a peripheral line due to the potential for infusion-related reactions during therapy initiation. May administer with a central line starting in Week 3.

Administer using an infusion set made of polyurethane, polybutadiene, PVC, PP, or PE that contains a flow regulator and an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone 0.2 micron filter. Prime the infusion set with either 5% dextrose or 0.9% sodium chloride.

Do not infuse concurrently in the same IV line as other medications.

Dilution

Dilute in 250 mL of 5% dextrose or 0.9% sodium chloride injection prior to IV infusion. The infusion bag must be made of one of the following materials: polyvinylchloride (PVC), polypropylene (PP), polyethylene (PE), or polyolefin blend (PP + PE).

Administer the diluted solution within 10 hours (inclusive of the infusion time) at room temperature (15–25°C).

Rate of Administration

Recommended infusion rates for amivantamab-vmjw administration are summarized in Table 2 and Table 3.

Table 2. Recommended Infusion Rates for Amivantamab-vmjw 1050 mg Dose.18
Week	Dose (per 250 mL bag)	Infusion Rate
Week 1, Day 1 (split dose infusion)	350 mg	Initially, 50 mL/hr; increase to 75 mL/hr after 2 hours in the absence of infusion-related reactions
Week 1, Day 2 (split dose infusion)	700 mg	Initially, 50 mL/hr; increase to 75 mL/hr after 2 hours in the absence of infusion-related reactions
Week 2	1050 mg	85 mL/hr
Week 3	1050 mg	125 mL/hr
Week 4	1050 mg	125 mL/hr
Subsequent weeks (starting in week 5, the dosing interval is every 2 weeks)	1050 mg	125 mL/hr

Table 3. Recommended Infusion Rates for Amivantamab-vmjw 1400 mg Dose.18
Week	Dose (per 250 mL bag)	Infusion Rate
Week 1, Day 1 (split dose infusion)	350 mg	Initially, 50 mL/hr; increase to 75 mL/hr after 2 hours in the absence of infusion-related reactions
Week 1, Day 2 (split dose infusion)	1050 mg	Initially, 35 mL/hr; increase to 50 mL/hr after 2 hours in the absence of infusion-related reactions
Week 2	1400 mg	65 mL/hr
Week 3	1400 mg	85 mL/hr
Week 4	1400 mg	125 mL/hr
Subsequent weeks (starting in week 5, the dosing interval is every 2 weeks)	1400 mg	125 mL/hr

Dosage

Adults

Non-small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

IV

The recommended dose is based on baseline body weight. Dose adjustments not required for subsequent body weight changes.

Recommended dose in patients with body weight <80 kg: 1050 mg.

Recommended dose in patients with body weight ≥80 kg: 1400 mg.

Administer the initial dose (Week 1) as a split infusion on Days 1 and 2 as described in Table 2 and Table 3. Give doses weekly for the first 4 weeks (total of 4 doses), then every 2 weeks starting in Week 5.

Administer until disease progression or unacceptable toxicity.

Dosage Modification for Toxicity

If adverse effects occur during amivantamab-vmjw therapy, temporarily interrupt therapy, reduce dosage, and/or permanently discontinue drug. If dosage modification is required, reduce the dosage as described in Table 4.

Table 4. Recommended Dosage Reductions for Amivantamab-vmjw Adverse Reactions.1
Body weight at baseline	Initial dose	First dose reduction	Second dose reduction	Third dose reduction
<80 kg	1050 mg	700 mg	350 mg	Discontinue therapy
≥80 kg	1400 mg	1050 mg	700 mg	Discontinue therapy

Temporarily interrupt therapy, reduce dosage, and/or permanently discontinue amivantamab therapy in patients experiencing certain adverse effects (see Table 5).

Table 5. Recommended Dosage Modifications and Management for Amivantamab-vmjw Toxicity.1
Adverse reaction and severity	Dosage modifications and management
Infusion-related reactions (Grade 1 to 2)	Stop infusion and monitor until symptom resolution. Resume infusion at 50% of the infusion rate at which the reaction occurred. Increase the infusion rate if there are no additional symptoms after 30 minutes. Give corticosteroid premedication before subsequent infusions.
Infusion-related reactions (Grade 3)	Stop infusion and administer supportive care medications. Monitor until resolution of symptoms. Resume infusion at 50% of the infusion rate at which the reaction occurred. Increase the infusion rate if there are no additional symptoms after 30 minutes. Give corticosteroid premedication before subsequent infusions. Permanently discontinue for recurrent Grade 3 infusion-related reactions.
Infusion-related reactions (Grade 4)	Permanently discontinue therapy.
Interstitial lung disease/pneumonitis (any grade)	Withhold therapy if interstitial lung disease/pneumonitis is suspected and permanently discontinue if confirmed.
Dermatologic adverse reactions including dermatitis acneiform, pruritus, dry skin (Grade 2)	Provide supportive care. Consider dose reduction if rash does not improve after 2 weeks.
Dermatologic adverse reactions (Grade 3)	Withhold therapy and provide supportive care. Resume therapy at a reduced dose upon recovery to ≤ Grade 2. Permanently discontinue therapy if there is no improvement within 2 weeks.
Dermatologic adverse reactions (Grade 4)	Permanently discontinue therapy.
Dermatologic adverse reactions (severe bullous, blistering or exfoliating skin conditions including toxic epidermal necrolysis [TEN])	Permanently discontinue therapy.
Other adverse reactions (Grade 3)	Withhold therapy until recovery to ≤Grade 1 or baseline. Resume at the same dose if recovery occurs in <1 week. Resume at a reduced dose if recovery occurs after 1 but within 4 weeks. Permanently discontinue therapy if recovery does not occur within 4 weeks.
Other adverse reactions (Grade 4)	Withhold therapy until recovery to ≤Grade 1 or baseline. Resume at a reduced dose if recovery occurs within 4 weeks. Permanently discontinue therapy if recovery does not occur within 4 weeks. Permanently discontinue therapy for recurrent Grade 4 reactions.

Special Populations

Hepatic Impairment

The manufacturer makes no specific dosage recommendations.

Renal Impairment

The manufacturer makes no specific dosage recommendations.

Geriatric Patients

The manufacturer makes no specific dosage recommendations.

Cautions for Amivantamab-vmjw

Contraindications

None.

Warnings/Precautions

Infusion-related Reactions

Amivantamab can cause infusion-related reactions (IRR).

Administer premedication with antihistamines, antipyretics, and glucocorticoids and infuse amivantamab as recommended. Administer amivantamab via a peripheral line during Week 1 and Week 2.

Monitor for IRR in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt the infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue amivantamab based on IRR severity.

Interstitial Lung Disease/Pneumonitis

Amivantamab can cause interstitial lung disease/pneumonitis.

Monitor for new or worsening symptoms of interstitial lung disease/pneumonitis (e.g., dyspnea, cough, fever). Immediately hold amivantamab in patients with suspected interstitial lung disease/pneumonitis and permanently discontinue if confirmed.

Dermatologic Reactions

Amivantamab can cause rash (including dermatitis acneiform), pruritus, and dry skin.

Instruct patients to limit sun exposure, wear protective clothing, and use broad spectrum UVA/UVB sunscreen during and for 2 months after treatment with amivantamab.

If a skin reaction develops, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider a dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, dose reduce, or permanently discontinue amivantamab depending on the severity of the dermatologic reaction.

Ocular Toxicity

Amivantamab can cause ocular toxicity.

Promptly refer patients with eye symptoms to an ophthalmologist. Withhold, dose reduce, or permanently discontinue amivantamab based on the severity of the ocular toxicity.

Embryofetal Toxicity

May cause fetal harm when administered to a pregnant woman. Impaired embryofetal development, embryolethality, and abortion have occurred in animals.

Advise female patients of reproductive potential to use effective contraception during treatment with amivantamab and for 3 months after the final dose. If used during pregnancy, apprise patient of the potential fetal harm.

Immunogenicity

Amivantamab is a therapeutic protein with potential for immunogenicity.

The effects of anti-drug antibodies on the pharmacokinetics, safety, and efficacy of amivantamab are unknown.

Specific Populations

Pregnancy

May cause fetal harm.

Lactation

Not known whether amivantamab or its metabolites are distributed into human milk, affect milk production, or affect nursing infants.

Women should not breastfeed while receiving the drug and for 3 months after the final dose.

Females and Males of Reproductive Potential

Verify the pregnancy status of females of reproductive potential prior to initiating therapy.

Utilize effective contraception during therapy and for 3 months after the last dose.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

In clinical trials, 41% of patients receiving amivantamab were ≥65 years of age, while 9% were ≥75 years of age; no overall differences in safety or efficacy relative to younger adults.

Hepatic Impairment

Clinically meaningful differences in pharmacokinetics not observed with mild hepatic impairment.

Not studied in moderate to severe hepatic impairment.

Renal Impairment

Clinically meaningful differences not observed with Cl_cr 29–276 mL/minute.

Not studied in severe renal impairment (Cl_cr 15–29 mL/minute).

Common Adverse Effects

Most common (≥20%) adverse reactions: rash, infusion-related reactions, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, vomiting.

Most common laboratory abnormalities (≥20%): decreased lymphocytes, decreased albumin, decreased phosphate, decreased potassium, increased alkaline phosphatase, increased glucose, increased gamma-glutamyl transferase, decreased sodium.

Drug Interactions

No drug interaction information is available for amivantamab. No formal clinical drug-drug interaction studies were performed, and no interactions with concomitant medications are expected.

Amivantamab-vmjw Pharmacokinetics

Absorption

Bioavailability

Amivantamab exposure increased proportionally over the dose range of 350–1750 mg (0.25–1.25 times the approved recommended dosage, respectively).

Steady state concentrations occurred by the 9th infusion.

Distribution

Extent

Not known whether amivantamab is distributed into human milk.

Elimination

Elimination Route

As an IgG1 antibody, amivantamab is not likely to be eliminated principally by renal excretion or by hepatic enzyme metabolism.

Half-life

Mean terminal half-life 11.3 ± 4.53 days.

Special Populations

Pharmacokinetics not affected by age (range 32–87 years), sex, race, creatinine clearance, or mild hepatic impairment.

Volume of distribution and clearance increase with increasing body weight. Exposure is 30–40% lower in patients with body weight ≥80 kg compared to patients with lower body weight. Exposure to amivantamab was similar between patients with body weight <80 kg who received 1050 mg and patients with body weight ≥80 kg who received 1400 mg.

Stability

Storage

Parenteral

Injection concentrate

2–8°C in original carton to protect from light; do not freeze.

Actions

Bispecific antibody to the epidermal growth factor receptor (EGFR) and the mesenchymal-epithelial transition (MET) receptor.
Disrupts EGFR and MET signaling functions through blocking ligand binding. Disrupts degradation of EGFR and MET in the presence of EGFR exon 20 insertion mutations, which allows tumor cells to be targeted for destruction.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).
Advise patients that amivantamab 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.
Advise patients of the risks of interstitial lung disease/pneumonitis. Advise patients to immediately contact their healthcare provider for new or worsening respiratory symptoms.
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 and for 2 months after treatment with amivantamab. Advise patients to apply alcohol-free emollient cream to dry skin.
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.
Advise patients of the risk of paronychia. Advise patients to contact their healthcare provider for signs or symptoms of paronychia.
Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with amivantamab and for 3 months after the final dose.
Advise women not to breast-feed during treatment with amivantamab and for 3 months after the final dose.
Advise patient to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Amivantamab-vmjw is obtained through a specialty distribution network. Contact manufacturer or consult the Janssen Medical Information website ([Web]) for specific availability information.