Amivantamab
Overview
Amivantamab is a fully human bispecific monoclonal antibody designed to target both epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition (MET) receptor pathways, which are frequently involved in tumour growth and resistance mechanisms in non-small cell lung cancer. By binding to both EGFR and MET receptors, amivantamab blocks receptor activation, promotes receptor degradation, and enhances immune-mediated tumour cell killing through antibody-dependent cellular cytotoxicity. This dual targeting approach helps overcome resistance associated with single-pathway inhibition. Amivantamab is administered intravenously and is primarily used in adult patients with advanced or metastatic non-small cell lung cancer harbouring specific EGFR mutations, particularly exon 20 insertion alterations. Its targeted mechanism and biologic nature make it a key therapy in precision oncology, especially for patients whose disease does not respond adequately to traditional tyrosine kinase inhibitors or chemotherapy.
Background and Date of Approval
Amivantamab received accelerated approval from the United States Food and Drug Administration on May 21, 2021, for adult patients with locally advanced or metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. This approval was based on results from the CHRYSALIS clinical trial demonstrating meaningful response rates. The European Medicines Agency granted marketing authorisation on December 9, 2021, for similar indications in this patient population. On March 1, 2024, the FDA granted traditional approval for this indication and also approved amivantamab in combination with carboplatin and pemetrexed as first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. Additional expanded approvals have followed based on ongoing clinical trials evaluating combination regimens in broader EGFR-mutated populations.
Uses
Amivantamab is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer harbouring EGFR exon 20 insertion mutations, particularly after progression on platinum-based chemotherapy. It is also used in combination with chemotherapy agents such as carboplatin and pemetrexed as first-line treatment in eligible patients. Emerging indications include use in combination regimens targeting other EGFR mutation subtypes, guided by molecular testing and oncologic assessment.
Administration
Amivantamab is administered as an intravenous infusion, with dosing based on body weight. Treatment is typically initiated with weekly infusions for the first four weeks, followed by administration every two weeks thereafter until disease progression or unacceptable toxicity. Premedication is commonly required to reduce the risk of infusion-related reactions. Dose adjustments or interruptions may be necessary depending on patient tolerance, adverse reactions, and clinical response.
Side Effects
Common side effects associated with amivantamab include infusion-related reactions, skin rash, paronychia, fatigue, edema, nausea, constipation, diarrhea, musculoskeletal pain, and decreased appetite. Dermatologic toxicities are particularly frequent due to EGFR pathway inhibition. The severity and frequency of these effects vary among patients and are generally manageable with supportive care and dose modification under medical supervision.
Warnings
Serious adverse reactions include severe infusion-related reactions, interstitial lung disease or pneumonitis, dermatologic toxicity including severe rash, and thromboembolic events. Ocular toxicity and hypersensitivity reactions may also occur. Treatment should be interrupted or discontinued in cases of severe or life-threatening toxicity. Amivantamab may cause embryo-fetal harm, and effective contraception is recommended during treatment and for a defined period after completion.
Precautions
Baseline evaluation should include assessment of pulmonary status and overall clinical condition prior to initiating therapy. Patients should be monitored closely for infusion-related reactions, particularly during initial doses. As a monoclonal antibody, amivantamab has limited classic cytochrome-mediated drug interactions, but caution is required when used in combination with other anticancer therapies due to overlapping toxicities. Live vaccines should generally be avoided during treatment.
Expert Tips
Patient selection should be based on confirmed EGFR mutation status, particularly exon 20 insertion alterations, using validated diagnostic tests. Careful monitoring during the first infusion is essential due to the high incidence of infusion-related reactions. Educate patients about early signs of pulmonary symptoms, severe skin reactions, and thromboembolic events. Pharmacists should ensure appropriate premedication protocols are followed and coordinate infusion schedules with oncology teams. Close multidisciplinary collaboration supports optimal management and timely adjustment of therapy based on response and tolerability.