amivantamab

A-mih-VAN-tuh-mab

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies, epidermal growth factor receptor egfr inhibitors, kinase inhibitors

High Alert

First-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (in combination with carboplatin and pemetrexed).
Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations in patients whose disease has progressed on or after platinum-based chemotherapy.
First-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations (in combination with lazertinib).
Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations in patients whose disease has progressed on or after treatment with an EFGR tyrosine kinase inhibitor (in combination with carboplatin and pemetrexed).

Acts as a kinase inhibitor that targets EGFR and mesenchymal-epithelial transition, including EGFR exon 20 insertion mutations, which ultimately reduces cancer cell growth.

Therapeutic effects:

Decreased progression of and improved progression-free survival of NSCLC.

Absorption: IV administration results in complete bioavailability.

Distribution: Not extensively distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: 11.3 days.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	unknown

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

CV: deep vein thrombosis (DVT), edema

Derm: dry skin, paronychia, pruritus, rash, TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: blepharitis, blurred vision, conjunctival redness, dry eye, keratitis, ocular itching, uveitis, vision impairment

Endo: hyperglycemia

F and E: hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia

GI: ↑liver enzymes, abdominal pain, constipation, hypoalbuminemia, nausea, stomatitis, vomiting

GU: ↑serum creatinine

Hemat: bleeding, lymphopenia

Metab: ↓appetite

MS: pain

Neuro: dizziness, fatigue, headache, peripheral neuropathy

Resp: cough, dyspnea, pneumonia, pulmonary embolism (PE), INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS

Misc: fever, infusion-related reactions

Drug-drug:

None reported.

First-Line Treatment of NSCLC with Exon 20 Insertion Mutations or Previously Treated NSCLC with Exon 19 Deletions or Exon 21 L858R Substitution Mutations

IV (Adults ≥80 kg): 1750 mg once weekly for 4 wk (on Wk 1, split infusion on Days 1 and 2; on Wk 2–4, give infusion on Day 1); then 2100 mg every 3 wk starting on Wk 7 (no dose during Wk 5 and 6). Administer after carboplatin and pemetrexed. Continue until disease progression or unacceptable toxicity.
IV (Adults <80 kg): 1400 mg once weekly for 4 wk (on Wk 1, split infusion on Days 1 and 2; on Wk 2–4, give infusion on Day 1); then 1700 mg every 3 wk starting on Wk 7 (no dose during Wk 5 and 6). Administer after carboplatin and pemetrexed. Continue until disease progression or unacceptable toxicity.

Previously Treated NSCLC with Exon 20 Insertion Mutations or First-Line Treatment of NSCLC with Exon 19 Deletions or Exon 21 L858R Substitution Mutations

IV (Adults ≥80 kg): 1400 mg once weekly for 5 wk (on Wk 1, split infusion on Days 1 and 2; on Wk 2–5, give infusion on Day 1); then 1400 mg every 2 wk starting on Wk 7 (no dose during Wk 6). If administered in combination with lazertinib, give amivantamab any time after giving lazertinib when given on the same day. Continue until disease progression or unacceptable toxicity.
IV (Adults <80 kg): 1050 mg once weekly for 5 wk (on Wk 1, split infusion on Days 1 and 2; on Wk 2–5, give infusion on Day 1); then 1050 mg every 2 wk starting on Wk 7 (no dose during Wk 6). If administered in combination with lazertinib, give amivantamab any time after giving lazertinib when given on the same day. Continue until disease progression or unacceptable toxicity.

Solution for injection: 50 mg/mL

Monitor for infusion-related reactions. Assess for fever, chills, nausea, chest discomfort, hypotension, or dyspnea. Monitor in health care setting with cardiopulmonary resuscitation medications and equipment are available. If Grade 1 or 2 infusion-related reactions occur, stop the infusion if infusion-related reaction is suspected and monitor patient until symptoms resolve. Resume the infusion at 50% of the infusion rate when the reaction occurred. If there are no additional symptoms after 30 min, the infusion rate may be escalated. Include corticosteroid with premedications for subsequent dose. If Grade 3 infusion-related reactions occur, stop infusion and administer supportive care medications. Monitor continuously until symptoms resolve. Resume the infusion at 50% of the infusion rate when the reaction occurred. If there are no additional symptoms after 30 min, the infusion rate may be escalated. Include corticosteroid with premedications for subsequent doses. For recurrent Grade 3 infusion-related reactions, permanently discontinue amivantamab. If Grade 4 infusion-related reactions occur, permanently discontinue amivantamab.
Assess for dermatologic toxicity (dermatitis acneiform, pruritus, dry skin, paronychia [nail inflammation]). If dermatologic reactions occur, start topical corticosteroids and topical and/or oral antibiotics. Refer patients with severe rash, atypical appearance or distribution, or lack of improvement within 2 wk to a dermatologist. For dry skin, apply alcohol-free emollient cream. If Grade 1 or 2 dermatologic reactions occur, initiate supportive care management. Reassess after 2 wk; if rash does not improve, consider dose ↓. If Grade 3 dermatologic reactions occur, hold amivantamab and initiate supportive care management. Add oral steroids and consider dermatologic consultation. Upon recovery to Grade ≤2, resume at ↓ dose. If no improvement within 2 wk, permanently discontinue amivantamab. If Grade 4 dermatologic reactions or severe bullous, blistering, or exfoliating skin conditions (TEN) occur, permanently discontinue amivantamab.
Assess for ocular toxicity (blurry vision, conjunctivitis, corneal injury). If any grade ocular toxicity occurs, refer patients to an ophthalmologist. Based on the severity, hold or ↓ dose, or permanently discontinue amivantamab.
Assess respiratory status for pulmonary toxicity (ILD/pneumonitis). If any grade ILD/pneumonitis occurs, hold therapy for suspected ILD/pneumonitis. Permanently discontinue amivantamab if ILD/pneumonitis is confirmed.
Assess for venous thromboembolic events such as DVT and PE (in combination with lazertinib). If Grade 2 or 3 venous thromboembolic events occur, hold 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 started. If Grade 4 or recurrent Grade 2 or 3 venous thromboembolic events occur despite therapeutic anticoagulation, permanently discontinue amivantamab (and hold lazertinib). 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.
Assess for other adverse reactions (musculoskeletal pain, edema). If Grade 3 adverse reactions occur, hold therapy until recovery to Grade ≤1. Resume at the same dose if recovery occurs within 1 wk. Resume at ↓ dose if recovery occurs after 1 wk but within 4 wk. Permanently discontinue amivantamab if recovery does not occur within 4 wk. If Grade 4 adverse reactions occur, hold therapy until recovery to Grade ≤1. Resume at ↓ dose if recovery occurs within 4 wk. Permanently discontinue amivantamab if recovery does not occur within 4 wk or for recurrent Grade 4 reactions.

Lab Test Considerations:

Verify negative pregnancy status before starting treatment.
Assess for EGFR or MET exon 14 skipping mutations.
Perform hepatitis B virus screening and management before treatment.
Monitor CBC, basic metabolic panel, liver enzymes, and renal function during therapy.
May ↑ glucose, liver enzymes, and serum creatinine.
May ↓ potassium, magnesium, sodium, phosphate, and albumin.

Before the first infusion (wk 1, day 1 and 2), administer premedications to reduce the risk of infusion-related reactions. When used in combination with lazertinib, administer anticoagulant prophylaxis to prevent venous thromboembolic events for the 1st 4 mo of amivantamab/lazertinib treatment (do not use warfarin).
Premedications: Before all doses, administer diphenhydramine 25–50 mg (or equivalent) and acetaminophen 650–1000 mg PO (30–60 min before) or IV (15–30 min before). Before Wk 1, Day 1, administer dexamethasone 20 mg IV (or equivalent) 45–60 min before. Before Wk 1, Day 2 (optional [as needed] for subsequent doses), administer dexamethasone 10 mg IV (or equivalent) 45–60 min before.
Dose Reductions for Adverse Reactions: If reaction occurs at dose of 1050 mg, ↓dose to 700 mg (1st ↓) and 350 mg (2nd ↓). If reaction occurs at dose of 1400 mg, ↓dose to 1050 mg (1st ↓) and 700 mg (2nd ↓). If reaction occurs at dose of 1750 mg,↓ dose to 1400 mg (1st ↓) and 1050 mg (2nd ↓). If reaction occurs at dose of 2100 mg,↓ dose to 1750 mg (1st ↓) and 1400 mg (2nd ↓). If a 3rd dose ↓ is needed, permanently discontinue amivantamab.

IV Administration:

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 0.9% NaCl) only before the start of amivantamab infusion. Use administration sets made of either polyurethane, polybutadiene, PVC, polypropylene, or polyethylene.
In Wk 1 (Days 1 and 2) and Wk 2, administer via a peripheral line (to ↓ the risk of infusion-related reactions during initial treatment). Subsequent infusions (after Wk 2) may be administered via central line.
Intermittent Infusion: Diluent: Inspect solution in the vial; should be pale yellow to colorless. Do not use if discolored or if visible particles are present. Determine appropriate dose volume and discard the equal volume from a 250 mL bag of D5W or 0.9% NaCl. Withdraw appropriate volume from vial and add to infusion bag. Gently invert bag to mix; do not shake. 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. Diluted solutions can be stored at room temperature and administered within 10 hr of preparation (including infusion time). Concentration: 2–20 mg/mL. Rate: Combination therapy with lazertinib or single-agent therapy; body weight <80 kg: Wk 1, Day 1 (split-dose infusion) dose 350 mg/250 mL: initial rate 50 mL/hr (subsequent infusion rate 75 mL/hr). Wk 1, Day 2 (split-dose infusion) dose 700 mg/250 mL: initial rate 50 mL/hr (subsequent infusion rate 75 mL/hr). Wk 2 dose 1050 mg/250 mL: rate 85 mL/hr. Wk 3, 4, and 5, dose 1050 mg/250 mL: rate 125 mL/hr. Wk 6: no amivantamab dose. Subsequent infusions (starting Wk 7; dosed every 2 wk), dose 1050 mg/250 mL: rate 125 mL/hr. Combination therapy with lazertinib or single-agent therapy; body weight ≥80 kg: Wk 1, Day 1 (split-dose infusion) dose 350 mg/250 mL: initial rate 50 mL/hr (subsequent infusion rate 75 mL/hr). Wk 1, Day 2 (split-dose infusion) dose 1050 mg/250 mL: initial rate 35 mL/hr (subsequent infusion rate 50 mL/hr). Wk 2 dose 1400 mg/250 mL: rate 65 mL/hr. Wk 3 dose 1400 mg/250 mL: rate 85 mL/hr. Wk 4 and 5 dose 1400 mg/250 mL: rate 125 mL/hr. Wk 6: no amivantamab dose. Subsequent infusions (starting Wk 7; dosed every 2 wk), dose 1400 mg/250 mL: rate 125 mL/hr. Combination therapy with carboplatin and pemetrexed; body weight <80 kg: Wk 1, day 1 (split-dose infusion) dose 350 mg/250 mL: initial rate 50 mL/hr (subsequent infusion rate 75 mL/hr). Wk 1, Day 2 (split-dose infusion) dose 1050 mg/250 mL: initial rate 33 mL/hr (subsequent infusion rate 50 mL/hr). Wk 2 dose 1400 mg/250 mL: rate 65 mL/hr. Wk 3 dose 1400 mg/250 mL: rate 85 mL/hr. Wk 4 dose 1400 mg/250 mL: rate 125 mL/hr. Wk 5 and 6: no amivantamab dose. Subsequent infusions (starting Wk 7; dosed every 3 wk), dose 1750 mg/250 mL: rate 125 mL/hr. Combination therapy with carboplatin and pemetrexed; body weight ≥80 kg: Wk 1, Day 1 (split-dose infusion) dose 350 mg/250 mL: initial rate 50 mL/hr (subsequent infusion rate 75 mL/hr). Wk 1, Day 2 (split-dose infusion) dose 1400 mg/250 mL: initial rate 25 mL/hr (subsequent infusion rate 50 mL/hr). Wk 2 dose 1750 mg/250 mL: rate 65 mL/hr. Wk 3 dose 1750 mg/250 mL: rate 85 mL/hr. Wk 4 dose 1750 mg/250 mL: rate 125 mL/hr. Wk 5 and 6: no amivantamab dose. Subsequent infusions (starting Wk 7; dosed every 3 wk), dose 2100 mg/250 mL: rate 125 mL/hr.
For subsequent infusion rates:↑ infusion rate to the subsequent infusion rate after 2 hr in the absence of infusion-related reactions. Total approximate infusion time is 4–6 hr for Wk 1, Day 1, and 6–8 hr for Wk 1, Day 2. Total approximate infusion time for subsequent doses is 2 hr.
Y-Site Incompatibility:
- Do not administer other drugs through same IV line.

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Advise patient about signs/symptoms of infusion-related reactions and that they may occur with the 1st infusion. Advise patient to notify health care professional immediately for any signs/symptoms of infusion-related reactions or new or worsening respiratory symptoms.
Advise patient about photosensitivity and that they should limit sun exposure during and for 2 mo after treatment. Advise patient to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Advise patients of the risk of dermatologic adverse reactions. Advise patient to apply alcohol-free (isopropanol-free, ethanol-free) emollient cream to ↓ the risk of skin reactions. Consider prophylactic measures (use of oral antibiotics) to ↓ the risk of these reactions.
Advise patient of the risk of ocular toxicity. Advise patient 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 health care professional for signs or symptoms of any infection or inflammation of the skin around the fingernails or toenails.
Educate patient about the risks of serious and life-threatening venous thromboembolic events, including DVT and PE, when amivantamab is used in combination with lazertinib. Advise patient that prophylactic anticoagulants are recommended to be used for the 1st 4 mo of treatment and to immediately contact health care professional for signs and symptoms of venous thromboembolism.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise patient not to breastfeed during treatment and for 3 mo after last dose. Advise patient who could become pregnant to use effective contraception during therapy and for 3 mo after the last amivantamab dose.

Decreased progression of and improved progression-free survival of NSCLC.

Rybrevant

NDC Code

57894- Janssen Biotech, Inc.
- 57894-501- Rybrevant
  - 57894-501-01- 1 VIAL, SINGLE-USE in 1 CARTON (57894-501-01) / 1 INJECTION in 1 VIAL, SINGLE-USE (57894-501-00)

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Code ⬆