Amivantamab interacts in the following cases:
No clinical data are available on the efficacy and safety of vaccinations in patients taking amivantamab. Avoid the use of live or live-attenuated vaccines while patients are taking amivantamab.
No formal studies of amivantamab in patients with hepatic impairment have been conducted. Based on population PK analyses, no dose adjustment is necessary for patients with mild hepatic impairment. Caution is required in patients with moderate or severe hepatic impairment as amivantamab has not been studied in this patient population. If treatment is started, patients should be monitored for adverse reactions with dose modifications per the recommendations above.
No formal studies of amivantamab in patients with renal impairment have been conducted. Based on population pharmacokinetic (PK) analyses, no dose adjustment is necessary for patients with mild or moderate renal impairment. Caution is required in patients with severe renal impairment as amivantamab has not been studied in this patient population. If treatment is started, patients should be monitored for adverse reactions with dose modifications per the recommendations.
There are no human data to assess the risk of amivantamab use during pregnancy. No animal reproductive studies were conducted to inform a drug-associated risk. Administration of EGFR and MET inhibitor molecules in pregnant animals resulted in an increased incidence of impairment of embryo-foetal development, embryo lethality, and abortion. Therefore, based on its mechanism of action and findings in animal models, amivantamab could cause foetal harm when administered to a pregnant woman. Amivantamab should not be given during pregnancy unless the benefit of treatment of the woman is considered to outweigh potential risks to the foetus. If the patient becomes pregnant while taking this medicinal product the patient should be informed of the potential risk to the foetus.
It is unknown whether amivantamab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which is decreasing to low concentrations soon afterwards. A risk to the breast-fed child cannot be excluded during this short period just after birth, although IgGs are likely to be degraded in the gastrointestinal tract of the breast-fed child and not absorbed. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from amivantamab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Women of child-bearing potential should use effective contraception during and for 3 months after cessation of amivantamab treatment.
There are no data on the effect of amivantamab on human fertility. Effects on male and female fertility have not been evaluated in animal studies.
Amivantamab may have moderate influence on the ability to drive and use machines (e.g., dizziness, fatigue, visual impairment). If patients experience treatment-related symptoms, including vision-related adverse reactions, affecting their ability to concentrate and react, it is recommended that they do not drive or use machines until the effect subsides.
In the dataset of amivantamab as monotherapy (N=380), 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 amivantamab 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%).
Table 1 summarises the adverse drug reactions that occurred in patients receiving amivantamab as monotherapy.
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 1050 mg (for patients <80 kg) or 1400 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 (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000); 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.
Table 1. Adverse reactions in patients receiving amivantamab as monotherapy:
| System organ class Adverse reaction | Frequency category | Any Grade (%) | Grade 3-4 (%) |
|---|---|---|---|
| Metabolism and nutrition disorders | |||
| Hypoalbuminaemia* | Very common | 31 | 2† |
| Decreased appetite | 16 | 0.5† | |
| Hypocalcaemia | 10 | 0.3† | |
| Hypokalaemia | Common | 9 | 2 |
| Hypomagnesaemia | 8 | 0 | |
| Nervous system disorders | |||
| Dizziness* | Very common | 13 | 0.3† |
| Eye disorders | |||
| Visual impairment* | Common | 3 | 0 |
| Growth of eyelashes* | 1 | 0 | |
| Other eye disorders* | 6 | 0 | |
| Keratitis | Uncommon | 0.5 | 0 |
| Uveitis | 0.3 | 0 | |
| Respiratory, thoracic and mediastinal disorders | |||
| Interstitial lung disease* | Common | 3 | 0.5† |
| Gastrointestinal disorders | |||
| Diarrhoea | Very common | 11 | 2† |
| Stomatitis* | 24 | 0.5† | |
| Nausea | 23 | 0.5† | |
| Constipation | 23 | 0 | |
| Vomiting | 12 | 0.5† | |
| Abdominal pain* | Common | 9 | 0.8† |
| Haemorrhoids | 3.7 | 0 | |
| Hepatobiliary disorders | |||
| Alanine aminotransferase increased | Very common | 15 | 2 |
| Aspartate aminotransferase increased | 13 | 1 | |
| Blood alkaline phosphatase increased | 12 | 0.5† | |
| Skin and subcutaneous tissue disorders | |||
| Rash* | Very common | 76 | 3† |
| Nail toxicity* | 47 | 2† | |
| Dry skin* | 19 | 0 | |
| Pruritus | 18 | 0 | |
| Toxic epidermal necrolysis | Uncommon | 0.3 | 0.3† |
| Musculoskeletal and connective tissue disorders | |||
| Myalgia | Very common | 11 | 0.3† |
| General disorders and administration site conditions | |||
| Oedema* | Very common | 26 | 0.8† |
| Fatigue* | 26 | 0.8† | |
| Pyrexia | 11 | 0 | |
| Injury, poisoning and procedural complications | |||
| Infusion related reaction | Very common | 67 | 2 |
* Grouped terms
† Grade 3 events only
In the dataset of amivantamab in combination with carboplatin and pemetrexed (N=301), the most frequent adverse reactions in all grades were rash (83%), neutropenia (57%), nail toxicity (53%), infusion related reactions (51%), fatigue (43%), stomatitis (39%), nausea (43%), thrombocytopenia (40%), constipation (40%), oedema (40%), decreased appetite (33%), hypoalbuminaemia (32%), alanine aminotransferase increased (26%), aspartate aminotransferase increased (23%), vomiting (22%), and hypokalaemia (20%). Serious adverse reactions included rash (2.7%), venous thromboembolism (2.3%), thrombocytopenia (2.3%) and ILD (2.0%). Eight percent of patients discontinued amivantamab due to adverse reactions. The most frequent adverse reactions leading to treatment discontinuation were IRR (2.7%), rash (2.3%), ILD (2.3%), and nail toxicity (1.0%).
Table 2 summarises the adverse drug reactions that occurred in patients receiving amivantamab in combination with chemotherapy.
The data reflects exposure to amivantamab in combination with carboplatin and pemetrexed in 301 patients with locally advanced or metastatic non-small cell lung cancer. Patients received amivantamab 1400 mg (for patients <80 kg) or 1750 mg (for patients ≥80 kg) weekly for 4 weeks. Starting at Week 7, patients received amivantamab 1750 mg (for patients <80 kg) or 2100 mg (for patients ≥80 kg) every 3 weeks. The median exposure to amivantamab in combination with carboplatin and pemetrexed was 7.7 months (range: 0.0 to 28.1 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 (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000); 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.
Table 2. Adverse reactions in patients receiving amivantamab in combination with carboplatin and pemetrexed:
| System organ class Adverse reaction | Frequency category | Any Grade (%) | Grade 3-4 (%) |
|---|---|---|---|
| Blood and lymphatic system disorders | |||
| Neutropenia | Very common | 57 | 39 |
| Thrombocytopenia | 40 | 12 | |
| Metabolism and nutrition disorders | |||
| Decreased appetite | Very common | 33 | 1.3 |
| Hypoalbuminaemia* | 32 | 3.7 | |
| Hypokalaemia | 20 | 6.6 | |
| Hypomagnesaemia | 13 | 1.3 | |
| Hypocalcaemia | 12 | 1.0 | |
| Nervous system disorders | |||
| Dizziness* | Common | 10 | 0.3 |
| Vascular disorders | |||
| Venous thromboembolism* | Very common | 14 | 3.0 |
| Eye disorders | |||
| Other eye disorders* | Common | 7.3 | 0 |
| Visual impairment* | 3.0 | 0 | |
| Growth of eyelashes | Uncommon | 0.3 | 0 |
| Keratitis | 0.3 | 0 | |
| Uveitis | 0.3 | 0 | |
| Respiratory, thoracic and mediastinal disorders | |||
| Interstitial lung disease* | Common | 2.3 | 1.7 |
| Gastrointestinal disorders | |||
| Nausea | Very common | 43 | 1.0 |
| Constipation | 40 | 0.3 | |
| Stomatitis* | 39 | 3.0 | |
| Vomiting | 22 | 2.0 | |
| Diarrhoea | 19 | 2.3 | |
| Abdominal pain* | Common | 11 | 0.3 |
| Haemorrhoids | 9.3 | 0.7 | |
| Hepatobiliary disorders | |||
| Alanine aminotransferase increased | Very common | 26 | 4.3 |
| Aspartate aminotransferase increased | 23 | 0.7 | |
| Blood alkaline phosphatase increased | Common | 10 | 0.3 |
| Skin and subcutaneous tissue disorders | |||
| Rash* | Very common | 83 | 14 |
| Nail toxicity* | 53 | 4.3 | |
| Dry skin* | 16 | 0 | |
| Pruritus | 10 | 0 | |
| Musculoskeletal and connective tissue disorders | |||
| Myalgia | Common | 5.0 | 0.7 |
| General disorders and administration site conditions | |||
| Fatigue* | Very common | 43 | 4.7 |
| Oedema* | 40 | 1.3 | |
| Pyrexia | 14 | 0 | |
| Injury, poisoning and procedural complications | |||
| Infusion related reaction | Very common | 50 | 3.0 |
* Grouped terms
In patients treated with amivantamab monotherapy, infusion-related reactions occurred in 67% of patients. 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.
In patients treated with amivantamab in combination with carboplatin and pemetrexed, infusion-related reactions occurred in 50% of patients. Greater than 94% of IRRs were Grade 1-2. A majority of IRRs occurred at the first infusion with a median time to onset of 60 minutes (range 0-7 hours), and the majority occurring within 2 hours of infusion start. Occasionally an IRR can occur at re-initiation of amivantamab after prolonged dose interruptions of more than 6 weeks.
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 treated with amivantamab monotherapy and 2.3 % of patients treated with amivantamab in combination with carboplatin and pemetrexed. 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.
Rash (including dermatitis acneiform), pruritus, and dry skin occurred in 86% of patients treated with amivantamab alone. 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. Nail toxicity occurred in patients treated with amivantamab. Most events were Grade 1 or 2, with Grade 3 nail toxicity occurring in 1.8% of patients.
Rash (including dermatitis acneiform), occurred in 83% of patients treated with amivantamab in combination with carboplatin and pemetrexed. Most cases were Grade 1 or 2, with Grade 3 rash events occurring in 14% of patients. Rash leading to amivantamab discontinuation occurred in 2.3% of patients. Rash usually developed within the first 4 weeks of therapy, with a median time to onset of 14 days. Nail toxicity occurred in patients treated with amivantamab in combination with carboplatin and pemetrexed. Most events were Grade 1 or 2, with Grade 3 nail toxicity occurring in 4.3% of patients.
Eye disorders, including keratitis (0.5%), occurred in 9% of patients treated with amivantamab alone. Other reported adverse reactions included growth of eyelashes, visual impairment, and other eye disorders. All events were Grade 1-2.
Eye disorders, including keratitis (0.3%), occurred in 11% of patients treated with amivantamab in combination with carboplatin and pemetrexed. Other reported adverse reactions included growth of eyelashes, visual impairment, uveitis, and other eye disorders. All events were Grade 1-2.
There are limited clinical data with amivantamab in patients 75 years of age or over. No overall differences in safety were observed between patients ≥65 years of age and patients <65 years of age.
As with all therapeutic proteins, there is the potential for immunogenicity. In clinical studies of patients with locally advanced or metastatic NSCLC treated with amivantamab, 4 of the 865 (0.5%) participants who were treated with amivantamab and evaluable for the presence of anti-drug antibodies (ADA), tested positive for treatment-emergent anti-amivantamab antibodies. There was no evidence of an altered pharmacokinetic, efficacy, or safety profile due to anti-amivantamab antibodies.
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