RYBREVANT

What it is

Amivantamab is a fully-human immunoglobulin G1 (IgG1)-based bispecific antibody directed against the epidermal growth factor (EGF) and mesenchymal-epidermal transition (MET) receptors, produced by a mammalian cell line using recombinant DNA technology. RYBREVANT is a concentrate for solution for infusion, available as a colourless to pale yellow preservative-free liquid concentrate for intravenous infusion after dilution. Each single-use vial contains 350 mg of amivantamab per 7 mL vial.

Approved indications

— In combination with lazertinib for the 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. — In combination with carboplatin and pemetrexed for the 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 for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with activating EGFR exon 20 insertion mutations. — As monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with activating EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

Dosing overview

The recommended dose regimen for RYBREVANT is once every two weeks (Q2W) when used as monotherapy or in combination with lazertinib, and once every three weeks (Q3W) when used in combination with carboplatin and pemetrexed. The initial dose is administered as a split across two infusions on Day 1 and Day 2 of Week 1. Dosing is weight-based; for patients with baseline body weight less than 80 kg, the maintenance dose is 1050 mg once every two weeks or 1750 mg once every three weeks, and for patients with body weight 80 kg or greater, the maintenance dose is 1400 mg once every two weeks or 2100 mg once every three weeks. RYBREVANT should be administered until disease progression or unacceptable toxicity.

Key safety warnings

Infusion-related reactions (IRRs) including anaphylaxis may occur in patients treated with RYBREVANT, with IRRs reported in 61% of patients, of which 93% were Grade 1–2. A majority of IRRs occurred at the first infusion with a median time to onset of 60 minutes. To reduce the risk of IRRs, premedicate with antihistamines, antipyretics, and glucocorticoids, and follow the infusion recommendations in the dosing section. Interstitial lung disease (ILD)/pneumonitis occurred in 2.7% of patients treated with RYBREVANT, including 0.1% fatal events. Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (for example, dyspnoea, cough, fever), and immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. In patients receiving RYBREVANT in combination with lazertinib, venous thromboembolic (VTE) events, including deep venous thrombosis and pulmonary embolism, occurred in 36% of patients, predominantly in the first four months of therapy, including 0.5% fatal events. When initiating treatment with RYBREVANT in combination with lazertinib, it is recommended to administer anticoagulant prophylaxis to prevent venous thromboembolic events for the first four months of treatment. Skin and nail reactions may occur in patients treated with RYBREVANT. Rash (including dermatitis acneiform), pruritis and dry skin occurred in patients treated with RYBREVANT, with most cases Grade 1 or 2, and Grade 3 events occurring in 15.5% of patients. When initiating treatment with RYBREVANT, consider prophylactic therapy to reduce the risk and severity of skin and nail reactions, including an oral antibiotic (doxycycline or minocycline, 100 mg twice daily) starting on Day 1 for the first 12 weeks of treatment, topical antibiotic lotion to the scalp, a non-comedogenic skin moisturiser on the face and whole body (except scalp), and 4% chlorhexidine solution to wash hands and feet, daily while on treatment.

Contraindications

RYBREVANT is contraindicated in patients with hypersensitivity to amivantamab or to any of the excipients.

PBS listing

RYBREVANT 350 mg in 7 mL concentrate for intravenous infusion is listed on the PBS under 4 items with authority required restriction at an ex-manufacturer price of A$1484.00.

Regulatory history

RYBREVANT concentrate for intravenous infusion 350 mg/7 mL was first listed on the Australian Register of Therapeutic Goods on 2022-12-01. The medicine received provisional approval for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy, based on objective response rate and duration of response in a single-arm study, with continued approval dependent on verification and description of benefit in a confirmatory study. In November 2024, the PBAC recommended RYBREVANT for non-small cell lung cancer with EGFR exon 20 insertion mutation-positive locally advanced or metastatic disease as an Authority Required listing, considered cost-effective with an incremental cost-effectiveness ratio of $55,000 to less than $75,000 per QALY gained. In March 2025, the PBAC did not recommend RYBREVANT for first-line treatment of patients with epidermal growth factor receptor mutated locally advanced or metastatic (Stage IIIB–IV) NSCLC. This medicine is subject to additional monitoring in Australia.