RYBREVANT

/ Janssen

Administer via peripheral line for Week 1 Day 1 and 2 and Week 2 to reduce the risk of infusion-related reactions.
When administering amivantamab in combination with carboplatin and pemetrexed, infuse pemetrexed first, carboplatin second, and amivantamab last.
When administering amivantamab in combination with lazertinib, administer lazertinib orally any time before the amivantamab infusion.
When administering amivantamab in combination with lazertinib, administer anticoagulant prophylaxis to prevent venous thromboembolic (VTE) events for the first four months of treatment.
See prescribing information for full details.

First-Line Treatment of NSCLC with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations
First-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an approved test, in combination with Lazertinib.
Previously Treated NSCLC with EGFR Exon 20 Insertion Mutations
Treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutation, as detected by an approved test, whose disease has progressed on or after platinum-based chemotherapy.
First line treatment of NSCLC with EGFR Exon 20 Insertion Mutations
First-line treatment of adult patients with locally advanced (not amenable to curative therapy) or metastatic (NSCLC) with activating EGFR Exon 20 insertion mutations. In combination with carboplatin and pemetrexed.
Previously Treated NSCLC with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations
Treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal-growth factor receptor (EGFR) Exon 19 deletions or Exon 21 L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI). In combination with carboplatin and pemetrexed.

Hypersensitivity to the active substance or to any of the excipients

Infusion Related Reactions
This medical product can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is approximately 1 hour.
Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse amivantamab as recommended. Administer via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion-related reactions.
Monitor patients for any signs and symptoms of infusion reactions during amivantamab infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue amivantamab based on severity.
Interstitial Lung Disease/Pneumonitis
Amivantamab can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.
Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold amivantamab in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.
Venous Thromboembolic (VTE) Events with Concomitant Use of Amivantamab and Lazertinib
Amivantamab in combination with lazertinib can cause serious and fatal venous thromboembolic (VTEs) events, including deep vein thrombosis and pulmonary embolism. The majority of these events occurred during the first four months of therapy. Withhold amivantamab and lazertinib based on severity. Once anticoagulant treatment has been initiated, resume amivantamab and lazertinib at the same dose level. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue amivantamab. Treatment can continue with lazertinib at the same dose level.
Dermatologic Adverse Reactions
Amivantamab can cause severe rash (including toxic epidermal necrolysis (TEN), dermatitis acneiform), pruritus and dry skin.
Instruct patients to limit sun exposure during and for 2 months after treatment with amivantamab. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream is recommended for dry skin. A prophylactic approach to rash prevention should be considered.
When initiating treatment with amivantamab, administer alcohol free (e.g., isopropanol-free, ethanol-free) emollient cream to reduce the risk of dermatologic adverse reactions. Consider prophylactic measures (e.g., use of oral antibiotics) to reduce the risk of dermatologic adverse reactions. If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider 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 based on severity.
Ocular Toxicity
REVANT can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus and uveitis.
Promptly refer patients with new or worsening eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue amivantamab based on severity.
Embryo-Fetal Toxicity
Based on its mechanism of action and findings from animal models, amivantamab can cause fetal harm when administered to a pregnant woman.
Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose.
See prescribing information for full details.

The most common adverse reactions (≥20%) were rash, nail toxicity, infusion-related reaction, musculoskeletal pain, stomatitis, edema, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, and nausea. The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, increased GGT and increased magnesium.
See prescribing information for full details.

Pregnancy: Based on the mechanism of action and findings in animal models, amivantamab can cause fetal harm when administered to a pregnant woman. There are no available data on the use of amivantamab in pregnant women or animal data to assess the risk of amivantamab in pregnancy. Pregnancy Testing
Verify pregnancy status of females of reproductive potential prior to initiating treatment. Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the  last dose.
Lactation: There are no data on the presence of amivantamab-vmjw in human milk , theeffects on the breastfed child or on milk production. Because of the potential for serious adverse reactions from amivantamab in breast-fed  children, advise women not to breast-feed during treatment with amivantamab and for 3 months after the last dose.