Rybrevant Adverse Reactions

Summary of the safety profile: The most frequent adverse reactions in all grades were rash (76%), infusion-related reactions (67%), nail toxicity (47%), hypoalbuminaemia (31%), oedema (26%), fatigue (26%), stomatitis (24%), nausea (23%), and constipation (23%). Serious adverse reactions included ILD (1.3%), IRR (1.1%), and rash (1.1%). Three percent of patients discontinued Rybrevant due to adverse reactions. The most frequent adverse reactions leading to treatment discontinuation were IRR (1.1%), ILD (0.5%), and nail toxicity (0.5%).
Tabulated list of adverse reactions: Table 7 summarises the adverse drug reactions that occurred in patients receiving amivantamab.
The data reflects exposure to amivantamab in 380 patients with locally advanced or metastatic non-small cell lung cancer after failure of platinum-based chemotherapy. Patients received amivantamab 1,050 mg (for patients < 80 kg) or 1,400 mg (for patients ≥ 80 kg). The median exposure to amivantamab was 4.1 months (range: 0.0 to 39.7 months).
Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (frequency cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. (See Table 7.)

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Description of selected adverse reactions: Infusion-related reactions: Infusion-related reactions occurred in 67% of patients treated with amivantamab. Ninety-eight percent of IRRs were Grade 1-2. Ninety-nine percent of IRRs occurred at the first infusion with a median time to onset of 60 minutes, and the majority occurring within 2 hours of infusion start. The most frequent signs and symptoms include chills, dyspnoea, nausea, flushing, chest discomfort, and vomiting (see Precautions).
Interstitial lung disease: Interstitial lung disease or ILD-like adverse reactions have been reported with the use of amivantamab as well as with other EGFR inhibitors. Interstitial lung disease or pneumonitis was reported in 2.6% of patients. Patients with a medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD were excluded from the clinical study (see Precautions).
Skin and nail reactions: Rash (including dermatitis acneiform), pruritus, and dry skin occurred in 76% of patients treated with amivantamab. Most cases were Grade 1 or 2, with Grade 3 rash events occurring in 3% of patients. Rash leading to amivantamab discontinuation occurred in 0.3% of patients. Rash usually developed within the first 4 weeks of therapy, with a median time to onset of 14 days. Paronychia occurred in patients treated with amivantamab. Most events were Grade 1 or 2, with Grade 3 paronychia occurring in 1.8% of patients (see Precautions).
Eye disorders: Eye disorders, including keratitis (0.5%), occurred in 9% of patients treated with amivantamab. Other reported adverse reactions included growth of eyelashes, visual impairment, and other eye disorders. All events were Grade 1-2 (see Precautions).
Other special populations: Elderly: There are limited clinical data with amivantamab in patients 75 years of age or over (see Pharmacology: Pharmacodynamics under Actions). No overall differences in safety were observed between patients ≥ 65 years of age and patients < 65 years of age.
Immunogenicity: As with all therapeutic proteins, there is the potential for immunogenicity. In a clinical study of patients with locally advanced or metastatic NSCLC treated with amivantamab, 3 (0.9%) of the 347 evaluable patients tested positive for anti-amivantamab antibodies. There was no evidence of an altered pharmacokinetic, efficacy, or safety profile due to anti-amivantamab antibodies.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.