Amivantamab: Drug information

For additional information see "Amivantamab: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US

Rybrevant

Brand Names: Canada

Rybrevant

Pharmacologic Category

Antineoplastic Agent, Epidermal Growth Factor Receptor (EGFR) Inhibitor;
Antineoplastic Agent, MET Inhibitor;
Antineoplastic Agent, Monoclonal Antibody

Dosing: Adult

Dosage guidance:

Safety: Premedications are recommended prior to infusion (to reduce the risk of infusion reaction). Administer alcohol-free (eg, isopropanol-free, ethanol-free) emollient cream and consider prophylactic measures (eg, oral antibiotics) to reduce the risk of dermatologic reactions. Advise patients to wear protective clothing, use broad spectrum UVA/UVB sunscreen, and limit sun exposure during and for 2 months after treatment.

Dosing: Dose is based on baseline body weight (dose adjustments are not required for subsequent changes in body weight).

Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 19 deletion or exon 21 L858R substitution mutation, first-line treatment

Non-small cell lung cancer, locally advanced or metastatic, with EGFR exon 19 deletion or exon 21 L858R substitution mutation, first-line treatment (combination therapy): Note: Select patients for amivantamab treatment based on the presence of epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations in tumor or plasma specimens (testing does not need to be repeated once EGFR status has been established). Administer anticoagulant prophylaxis to prevent venous thromboembolic events for the first 4 months of treatment; use of vitamin K antagonists is not recommended. Consider discontinuation of anticoagulant prophylaxis if there are no signs or symptoms of venous thromboembolism during the first 4 months of treatment.

**Recommended Amivantamab Dosage (in Combination with Lazertinib)**
Body weight (at baseline)	Dose and schedule^a
<80 kg	Week 1: IV: 1,050 mg split over days 1 and 2 (350 mg on day 1 and 700 mg on day 2). Weeks 2 to 5: IV: 1,050 mg once weekly. Week 6: No amivantamab dose. Subsequent infusions (starting at week 7): IV: 1,050 mg once every 2 weeks until disease progression or unacceptable toxicity.
≥80 kg	Week 1: IV: 1,400 mg split over days 1 and 2 (350 mg on day 1 and 1,050 mg on day 2). Weeks 2 to 5: IV: 1,400 mg once weekly. Week 6: No amivantamab dose. Subsequent infusions (starting at week 7): IV: 1,400 mg once every 2 weeks until disease progression or unacceptable toxicity.
^a Cho 2024; manufacturer’s labeling.

Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 19 deletion or exon 21 L858R substitution mutation, previously treated

Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 19 deletion or exon 21 L858R substitution mutation, previously treated (combination therapy): Note: Select patients for amivantamab treatment based on the presence of epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations in tumor or plasma specimens (testing does not need to be repeated once EGFR status has been established).

**Recommended Amivantamab Dosage (in Combination with Pemetrexed and Carboplatin)**
Body weight (at baseline)	Dose and schedule^a,b
^a Administer amivantamab per dosing table above (in combination with pemetrexed and carboplatin) every 3 weeks for up to 4 cycles, followed by amivantamab and pemetrexed every 3 weeks until disease progression or unacceptable toxicity.
^bPassaro 2024; manufacturer’s labeling.
<80 kg	Week 1: IV: 1,400 mg split over days 1 and 2 (350 mg on day 1 and 1,050 mg on day 2). Weeks 2 to 4: IV: 1,400 mg once weekly. Weeks 5 and 6: No amivantamab dose. Subsequent infusions (starting at week 7): IV: 1,750 mg once every 3 weeks.
≥80 kg	Week 1: IV: 1,750 mg split over days 1 and 2 (350 mg on day 1 and 1,400 mg on day 2). Weeks 2 to 4: IV: 1,750 mg once weekly. Weeks 5 and 6: No amivantamab dose. Subsequent infusions (starting at week 7): IV: 2,100 mg once every 3 weeks.

Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 20 insertion mutation, first-line treatment

Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 20 insertion mutation, first-line treatment (combination therapy): Note: Select patients for amivantamab treatment based on the presence of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in tumor or plasma specimens (testing does not need to be repeated once EGFR status has been established).

**Recommended Amivantamab Dosage (in Combination With Pemetrexed and Carboplatin)**
Body weight (at baseline)	Dose and schedule^a,b
^a Administer amivantamab per dosing table above (in combination with pemetrexed and carboplatin) every 3 weeks for up to 4 cycles, followed by amivantamab and pemetrexed every 3 weeks until disease progression or unacceptable toxicity.
^bZhou 2023; manufacturer’s labeling.
<80 kg	Week 1: IV: 1,400 mg split over days 1 and 2 (350 mg on day 1 and 1,050 mg on day 2). Weeks 2 to 4: IV: 1,400 mg once weekly. Weeks 5 and 6: No amivantamab dose. Subsequent infusions (starting at week 7): IV: 1,750 mg once every 3 weeks.
≥80 kg	Week 1: IV: 1,750 mg split over days 1 and 2 (350 mg on day 1 and 1,400 mg on day 2). Weeks 2 to 4: IV: 1,750 mg once weekly. Weeks 5 and 6: No amivantamab dose. Subsequent infusions (starting at week 7): IV: 2,100 mg once every 3 weeks.

Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 20 insertion mutation, previously treated

Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 20 insertion mutation, previously treated (single-agent therapy): Note: Select patients for amivantamab treatment based on the presence of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in tumor or plasma specimens (testing does not need to be repeated once EGFR status has been established).

**Recommended Amivantamab Dosage (Single-Agent Therapy)**
Body weight (at baseline)	Dose and schedule^a
^a Park 2021; manufacturer’s labeling.
<80 kg	Week 1: IV: 1,050 mg split over days 1 and 2 (350 mg on day 1 and 700 mg on day 2). Weeks 2 to 5: IV: 1,050 mg once weekly. Week 6: No amivantamab dose. Subsequent infusions (starting at week 7): IV: 1,050 mg once every 2 weeks until disease progression or unacceptable toxicity.
≥80 kg	Week 1: IV: 1,400 mg split over days 1 and 2 (350 mg on day 1 and 1,050 mg on day 2). Weeks 2 to 5: IV: 1,400 mg once weekly. Week 6: No amivantamab dose. Subsequent infusions (starting at week 7): IV: 1,400 mg once every 2 weeks until disease progression or unacceptable toxicity.

Premedication:

**Amivantamab Premedications**
Medication	Dose	Administration route	Dosing window (prior to amivantamab)
Antihistamine (administer prior to all amivantamab doses)	Diphenhydramine (25 to 50 mg) or equivalent	IV	15 to 30 minutes
Antihistamine (administer prior to all amivantamab doses)	Diphenhydramine (25 to 50 mg) or equivalent	Oral	30 to 60 minutes
Antipyretic (administer prior to all amivantamab doses)	Acetaminophen 650 to 1,000 mg	IV	15 to 30 minutes
Antipyretic (administer prior to all amivantamab doses)	Acetaminophen 650 to 1,000 mg	Oral	30 to 60 minutes
Glucocorticoid (administer prior to week 1, day 1)	Dexamethasone (20 mg) or equivalent	IV	45 to 60 minutes
Glucocorticoid (administer prior to week 1, day 2; optional [as needed] for subsequent doses)	Dexamethasone (10 mg) or equivalent	IV	45 to 60 minutes

Missed doses: If a dose is missed or withheld for >1 month and it is clinically appropriate to resume amivantamab, consider reinitiation with weekly dosing, beginning with the first dose split over days 1 and 2 (eg, as dosed in cycle 1, days 1 and 2) (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

eGFR ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, eGFR 30 to 89 mL/minute had no clinically meaningful difference on amivantamab pharmacokinetics.

eGFR 15 to 29 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

End-stage kidney disease (eGFR <15 mL/minute): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Liver Impairment: Adult

Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to ≤1.5 times ULN): There are no dosage adjustments provided in the manufacturer’s labeling; however, mild impairment had no clinically meaningful difference on amivantamab pharmacokinetics.

Moderate or severe impairment (total bilirubin >1.5 times ULN and any AST): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Adjustment for Toxicity: Adult

Note: Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation. When administered in combination with lazertinib, if an adverse effect requires dose reduction after withholding treatment and resolution, upon resumption of therapy, the dose of amivantamab should be reduced first.

**Amivantamab Dosage Reduction Levels**
Dose (at which adverse reaction occurred)	1,050 mg	1,400 mg	1,750 mg	2,100 mg
1^st dose reduction	700 mg	1,050 mg	1,400 mg	1,750 mg
2^nd dose reduction	350 mg	700 mg	1,050 mg	1,400 mg
3^rd dose reduction	Discontinue amivantamab.

**Amivantamab Dosage Modification for Adverse Reactions**
Adverse reaction	Severity	Dosage modification
^a VTE = venous thromboembolic events
Dermatologic toxicity (including dermatitis acneiform, pruritus, dry skin)	General recommendations	If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist.
	Dry skin	Apply alcohol-free emollient cream.
	Grade 1 or 2	Initiate supportive care management. Reassess after 2 weeks; if rash does not improve, consider amivantamab dose reduction.
	Grade 3	Withhold amivantamab and initiate supportive care management. Add oral steroids and consider dermatologic consultation. Upon recovery to ≤ grade 2, resume amivantamab at reduced dose. If no improvement within 2 weeks, permanently discontinue amivantamab.
	Grade 4	Permanently discontinue amivantamab.
	Severe bullous, blistering, or exfoliating skin conditions (including toxic epidermal necrolysis)	Permanently discontinue amivantamab.
Ocular toxicity	Any grade	Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Based on the severity, withhold, dose reduce, or permanently discontinue amivantamab.
Pulmonary toxicity: Interstitial lung disease (ILD)/pneumonitis	Any grade	Withhold amivantamab for suspected ILD/pneumonitis. Permanently discontinue amivantamab if ILD/pneumonitis is confirmed.
Infusion-related reaction (IRR)	Grade 1 or 2	Interrupt amivantamab infusion for suspected IRR and monitor until reaction symptoms resolve. Resume the infusion at 50% of the infusion rate at which the reaction occurred. If there are no additional symptoms after 30 minutes, the infusion rate may be escalated (see Administration). Include corticosteroid with premedications for subsequent doses.
	Grade 3	Interrupt amivantamab infusion and administer supportive care medications. Monitor continuously until reaction symptoms resolve. Resume the infusion at 50% of the infusion rate at which the reaction occurred. If there are no additional symptoms after 30 minutes, the infusion rate may be escalated (see Administration). Include corticosteroid with premedications for subsequent doses.
	Grade 3 (recurrent)	Permanently discontinue amivantamab.
	Grade 4	Permanently discontinue amivantamab.
	Anaphylaxis/anaphylactic reactions (any grade)	Permanently discontinue amivantamab.
VTE^a (in combination with lazertinib)	Grade 2 or 3	Withhold amivantamab (and lazertinib) and administer anticoagulant treatment as clinically indicated. Resume amivantamab (and lazertinib) at the same dose level at the discretion of the health care provider once anticoagulation treatment has been initiated.
VTE^a (in combination with lazertinib)	Grade 4 or recurrent grade 2 or 3 despite therapeutic anticoagulation	Permanently discontinue amivantamab (and withhold lazertinib) and administer anticoagulant treatment as clinically indicated. Resume lazertinib at the same dose level at the discretion of the health care provider once anticoagulation treatment has been initiated.
Other adverse reactions	Grade 3	Withhold amivantamab until recovery to ≤ grade 1 or baseline. Resume at the same dose if recovery occurs within 1 week. Resume at reduced dose if recovery occurs after 1 week but within 4 weeks. Permanently discontinue amivantamab if recovery does not occur within 4 weeks.
Other adverse reactions	Grade 4	Withhold amivantamab until recovery to ≤ grade 1 or baseline. Resume at reduced dose if recovery occurs within 4 weeks. Permanently discontinue amivantamab if recovery does not occur within 4 weeks or for recurrent grade 4 reactions.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions (Significant): Considerations

Dermatologic toxicity

Amivantamab may cause skin rash (including acneiform dermatitis), pruritus, and xeroderma. Rash has been observed in patients treated with amivantamab, including grade 3 rash. Erosive pustular dermatosis, IgA bullous dermatitis, paronychia, and toxic epidermal necrolysis have also been reported (Ref).

Onset: Varied; median: 14 days (range: 1 to 276 days).

Risk factors:

• Dose (potential risk factor)

Infusion-related reactions

Amivantamab may cause an infusion-related reaction (IRR), including anaphylaxis. IRRs occurred in approximately two-thirds of patients treated with amivantamab, particularly with the first infusion. Most IRRs were grade 1 or 2; however, grade 3 and 4 IRRs have been reported.

Mechanism: Non–dose-related; immunologic.

Onset: Rapid; median: 1 hour (range: 0.1 to 18 hours) after initiation of infusion. The vast majority of IRRs occurred with the week 1 day 1 infusion, with a much smaller incidence occurring on week 1 day 2 and only a small percentage occurring with subsequent infusions.

Risk factors:

• Infusion rate

• Omission of premedication (potential risk factor)

Ocular toxicity

Amivantamab may cause ocular toxicity, including keratitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, and uveitis. All reported ocular adverse events were grade 1 or 2.

Risk factors:

• Dose (potential risk factor)

Pulmonary toxicity

Interstitial lung disease (ILD)/pneumonitis, including grade 3 events, have been reported. Symptoms of pneumonitis typically present as cough, dyspnea, and fever; permanent discontinuation is warranted if ILD/pneumonitis is confirmed.

Risk factors:

• Dose (potential risk factor)

Venous thromboembolic events

Amivantamab, in combination with lazertinib, may cause serious and fatal venous thromboembolic events (VTEs), including deep vein thrombosis and pulmonary embolism. VTEs were reported in 36% of patients receiving amivantamab in combination with lazertinib in clinical trials, including grade 3 and 4 events. VTEs may lead to dose interruption, dose reduction, and/or permanent discontinuation of therapy.

Mechanism: Not clearly established; transitory prothrombotic state caused by rapid tumor-cell death by amivantamab and lazertinib has been hypothesized.

Onset: Varied; median: 84 days (range: 6 to 777 days). In general, events occur during the first 4 months of therapy.

Risk factors:

• Omission of anticoagulant prophylaxis (Ref)

• Tumor response (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Cardiovascular: Edema (27%)

Dermatologic: Paronychia (50%), pruritus (18%), skin rash (84%), xeroderma (14%)

Endocrine & metabolic: Decreased serum albumin (79%), decreased serum magnesium (27%), decreased serum phosphate (33%), decreased serum potassium (26%), decreased serum sodium (27%), increased serum glucose (56%)

Gastrointestinal: Abdominal pain (11%), constipation (23%), decreased appetite (15%), diarrhea (16%; grades 3/4: 3%), nausea (36%), stomatitis (26%; grades 3/4: <1%), vomiting (22%)

Hematologic & oncologic: Hemorrhage (19%), lymphocytopenia (36%; grades 3/4: 8%)

Hepatic: Increased gamma-glutamyl transferase (27%), increased serum alanine aminotransferase (38%), increased serum alkaline phosphatase (53%), increased serum aspartate aminotransferase (33%)

Hypersensitivity: Infusion-related reaction (64%)

Nervous system: Dizziness (12%), fatigue (33%), peripheral neuropathy (13%)

Neuromuscular & skeletal: Musculoskeletal pain (47%)

Renal: Increased serum creatinine (46%)

Respiratory: Cough (25%), dyspnea (37%)

Miscellaneous: Fever (13%)

1% to 10%:

Dermatologic: Toxic epidermal necrolysis (<10%)

Nervous system: Headache (10%)

Ophthalmic: Ocular toxicity (<10%)

Respiratory: Interstitial lung disease (<10%), pneumonia (10%), pneumonitis (<10%)

Frequency not defined:

Cardiovascular: Pulmonary embolism

Immunologic: Antibody development

Nervous system: Myasthenia

Ophthalmic: Keratitis, uveitis

Respiratory: Pleural effusion

Postmarketing:

Dermatologic: Bullous dermatitis (linear IgA) (Ref), pustular rash (erosive pustular dermatosis) (Ref)

Genitourinary: Genital lesion (inguinal and penile ulceration) (Ref)

Hypersensitivity: Anaphylaxis

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to amivantamab or any component of the formulation.

Warnings/Precautions

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Appropriate use: Select patients for amivantamab treatment based on the presence of epidermal growth factor receptor (EGFR) exon 20 insertion mutations (first-line treatment [in combination with pemetrexed and carboplatin] or previously treated [as a single agent]) or EGFR exon 19 deletions/exon 21 L858R substitution mutations (first-line treatment [in combination with lazertinib] or previously treated [in combination with pemetrexed and carboplatin]) in tumor or plasma specimens. Information on approved tests is available at http://www.FDA.gov/CompanionDiagnostics.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Rybrevant: Amivantamab-vmjw 350 mg/7 mL (7 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]

Generic Equivalent Available: US

Pricing: US

Solution (Rybrevant Intravenous)

350 mg/7 mL (per mL): $652.57

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Rybrevant: Amivantamab-vmjw 350 mg/7 mL (7 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]

Administration: Adult

IV: Administer according to the infusion rate(s) in the Amivantamab Recommended Administration Rate table. Administer via an infusion set fitted with a flow regulator and with an in-line, sterile, nonpyrogenic, low protein-binding polyethersulfone 0.2 micron filter; administration set with filter must be primed with diluent (D5W or NS) only prior to the initiation of amivantamab infusion. Use administration sets made of either polyurethane, polybutadiene, PVC, polypropylene, or polyethylene.

In week 1 (days 1 and 2) and week 2, administer via a peripheral line (to reduce the risk of infusion-related reactions during initial treatment). Subsequent infusions (after week 2) may be administered via central line. Prepare the initial amivantamab infusion as close to administration time as possible to allow for potential extended infusion times if an infusion-related reaction occurs. Do not infuse amivantamab concomitantly in the same IV line with other medications.

Premedications are recommended to reduce the risk of infusion-related reactions. When used in combination with lazertinib, anticoagulant prophylaxis is recommended for the first 4 months (do not use a vitamin K antagonist).

Administration sequence (for combination therapy):

In combination with pemetrexed and carboplatin: Administer pemetrexed first, carboplatin second, then amivantamab last.

In combination with lazertinib: When administered on the same day, administer lazertinib any time prior to amivantamab.

**Amivantamab Recommended Administration Rate**
^a Increase the infusion rate to the subsequent infusion rate after 2 hours in the absence of infusion-related reactions. Total approximate infusion time is 4 to 6 hours for week 1, day 1 and 6 to 8 hours for week 1, day 2. Total approximate infusion time for subsequent doses is 2 hours.
Combination therapy with lazertinib or single-agent therapy; body weight <80 kg (1,050 mg dose)
Week	Dose (per 250 mL bag)	Initial infusion rate	Subsequent infusion rate^a
Week 1, day 1 (split-dose infusion)	350 mg	50 mL/hour	75 mL/hour
Week 1, day 2 (split-dose infusion)	700 mg	50 mL/hour	75 mL/hour
Week 2	1,050 mg	85 mL/hour
Week 3	1,050 mg	125 mL/hour
Week 4	1,050 mg	125 mL/hour
Week 5	1,050 mg	125 mL/hour
Week 6	No amivantamab dose
Subsequent infusions (starting week 7; dosed every 2 weeks)	1,050 mg	125 mL/hour
Combination therapy with lazertinib or single-agent therapy; body weight ≥80 kg (1,400 mg dose)
Week	Dose (per 250 mL bag)	Initial infusion rate	Subsequent infusion rate^a
Week 1, day 1 (split-dose infusion)	350 mg	50 mL/hour	75 mL/hour
Week 1, day 2 (split-dose infusion)	1,050 mg	35 mL/hour	50 mL/hour
Week 2	1,400 mg	65 mL/hour
Week 3	1,400 mg	85 mL/hour
Week 4	1,400 mg	125 mL/hour
Week 5	1,400 mg	125 mL/hour
Week 6	No amivantamab dose
Subsequent infusions (starting week 7; dosed every 2 weeks)	1,400 mg	125 mL/hour
Combination therapy with pemetrexed and carboplatin; body weight <80 kg (1,750 mg dose)
Week	Dose (per 250 mL bag)	Initial infusion rate	Subsequent infusion rate^a
Week 1, day 1 (split-dose infusion)	350 mg	50 mL/hour	75 mL/hour
Week 1, day 2 (split-dose infusion)	1,050 mg	33 mL/hour	50 mL/hour
Week 2	1,400 mg	65 mL/hour
Week 3	1,400 mg	85 mL/hour
Week 4	1,400 mg	125 mL/hour
Weeks 5 and 6	No amivantamab dose
Subsequent infusions (starting week 7; dosed every 3 weeks)	1,750 mg	125 mL/hour
Combination therapy with pemetrexed and carboplatin; body weight ≥80 kg (2,100 mg dose)
Week	Dose (per 250 mL bag)	Initial infusion rate	Subsequent infusion rate^a
Week 1, day 1 (split-dose infusion)	350 mg	50 mL/hour	75 mL/hour
Week 1, day 2 (split-dose infusion)	1,400 mg	25 mL/hour	50 mL/hour
Week 2	1,750 mg	65 mL/hour
Week 3	1,750 mg	85 mL/hour
Week 4	1,750 mg	125 mL/hour
Weeks 5 and 6	No amivantamab dose
Subsequent infusions (starting week 7; dosed every 3 weeks)	2,100 mg	125 mL/hour

Use: Labeled Indications

Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 19 deletion or exon 21 L858R substitution mutation, first-line treatment: First-line treatment (in combination with lazertinib) of locally advanced or metastatic non–small cell lung cancer (NSCLC) in adults with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations (as detected by an approved test).

Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 19 deletion or exon 21 L858R substitution mutation, previously treated: Treatment (in combination with pemetrexed and carboplatin) of locally advanced or metastatic NSCLC in adults with EGFR exon 19 deletions or exon 21 L858R substitution mutations, with disease progression on or after treatment with an EGFR tyrosine kinase inhibitor.

Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 20 insertion mutation, first-line treatment: First-line treatment (in combination with pemetrexed and carboplatin) of locally advanced or metastatic NSCLC in adults with EGFR exon 20 insertion mutations (as detected by an approved test).

Non–small cell lung cancer, locally advanced or metastatic, with EGFR exon 20 insertion mutation, previously treated: Treatment (as a single agent) of locally advanced or metastatic NSCLC in adults with EGFR exon 20 insertion mutations (as detected by an approved test) with disease progression on or after platinum-based chemotherapy.

Medication Safety Issues

Sound-alike/look-alike issues:

Amivantamab may be confused with afatinib, avapritinib, naxitamab, tafasitamab.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Reproductive Considerations

Verify pregnancy status prior to treatment initiation.

Patients who could become pregnant should use effective contraception during therapy and for 3 months after the last amivantamab dose.

Pregnancy Considerations

Based on the mechanism of action and data from animal models, in utero exposure to amivantamab may cause fetal harm.

Amivantamab is a humanized monoclonal antibody (IgG₁). Human IgG is known to cross the placenta; exposure is dependent upon the IgG subclass, maternal serum concentrations, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Breastfeeding Considerations

It is not known if amivantamab is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 3 months after the last amivantamab dose.

Monitoring Parameters

EGFR exon 20 insertion mutation status in tumor or plasma specimens or EGFR exon 19 deletion or exon 21 L858R substitution mutation in tumor or plasma specimens. Evaluate pregnancy status prior to treatment (in patients who could become pregnant). Monitor for signs/symptoms of dermatologic toxicity, ocular toxicity, and for new or worsening symptoms (eg, dyspnea, cough, fever) indicative of interstitial lung disease/pneumonitis. Monitor (in a setting where cardiopulmonary resuscitation medication and equipment are available) for signs/symptoms of infusion reactions/anaphylaxis during infusion (eg, dyspnea, flushing, fever, chills, nausea, vomiting, chest discomfort, hypotension); monitor until resolved if a reaction occurs. Monitor for signs/symptoms of venous thromboembolic events (eg, deep vein thrombosis or pulmonary embolism; in combination with lazertinib).

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]).

Mechanism of Action

Amivantamab is a bispecific antibody that targets both epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET). Amivantamab binds to the EGFR and MET extracellular domains and disrupts EGFR and MET signaling by blocking ligand binding and, in exon 19 deletions, exon 21 L858R substitutions, and exon 20 insertion mutation models, degrading EGFR and MET. The presence of EGFR and MET on tumor cell surfaces also allows for targeted cell destruction by immune effector cells, such as natural killer cells and macrophages, via antibody-dependent cellular cytotoxicity and trogocytosis mechanisms, respectively. Amivantamab in combination with lazertinib increased in vivo antitumor activity when compared with either agent alone in animal non–small cell lung cancer models with EGFR L858R mutation.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_d: 5 L.

Half-life elimination: 14 days.

Excretion: Clearance: 0.26 L/day.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Body weight: Increases in body weight increased the amivantamab V_d and clearance. Amivantamab exposures are 30% to 40% lower in patients weighing ≥80 kg, compared to patients weighting <80 kg (at the same dose). Amivantamab exposures were comparable between patients who weighed <80 kg and received a 1,050 mg dose and patients who weighed ≥80 kg and received a 1,400 mg dose.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(QA) Qatar: Rybrevant

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George MN, Seervai RNH, Chon SY. Erosive pustular dermatosis-like eruption of the scalp secondary to amivantamab: a case series. JAAD Case Rep. 2024;47:72-79. doi:10.1016/j.jdcr.2023.11.027 [PubMed 38659476]
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J&J Medical Connect. Rybrevant - Dosage and Administration - Restarting after prolonged treatment interruption. https://www.jnjmedicalconnect.com/products/rybrevant/medical-content/rybrevant-dosage-and-administration-restarting-after-prolonged-treatment-interruption#references-content. Updated February 21, 2025. Accessed March 24, 2025.
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Park K, Haura EB, Leighl NB, et al. Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: initial results from the CHRYSALIS phase I study. J Clin Oncol. Published online August 2, 2021. doi:10.1200/JCO.21.00662 [PubMed 34339292]
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Refer to manufacturer's labeling.
Rybrevant (amivantamab) [prescribing information]. Horsham, PA: Janssen Biotech Inc; February 2025.
Rybrevant (amivantamab) [product monograph]. Toronto, Ontario, Canada: Janssen Inc; June 2024.
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Zhou C, Tang KJ, Cho BC, et al. Amivantamab plus chemotherapy in NSCLC with EGFR Exon 20 insertions. N Engl J Med. 2023;389(22):2039-2051. doi:10.1056/NEJMoa2306441 [PubMed 37870976]

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Amivantamab: Drug information