Amivantamab

Amivantamab is a targeted anticancer medicine belonging to the bispecific monoclonal antibody class and is directed against epidermal growth factor receptor and MET. It binds to these receptors on cancer cells, interfering with signaling pathways that can promote tumor-cell growth, survival and spread. Its antibody activity can also recruit immune cells to help destroy targeted cancer cells. Amivantamab is primarily used for adults with advanced or metastatic non-small cell lung cancer carrying specific activating EGFR mutations, including exon 20 insertion mutations and, in appropriate settings, exon 19 deletions or exon 21 L858R substitution mutations. Depending on the indication and regulatory jurisdiction, it may be administered alone or in combination with lazertinib, carboplatin and pemetrexed. Amivantamab is available as an intravenous formulation and, in the United States and applicable jurisdictions, as a subcutaneous formulation combined with recombinant human hyaluronidase. Treatment schedules depend on the indication, formulation, body weight and combination regimen. Important monitoring includes infusion-related reactions, venous thromboembolic events in certain combination settings, skin and nail toxicity, interstitial lung disease or pneumonitis, eye-related complications and other treatment-related adverse effects.

Amivantamab was developed as a fully human bispecific antibody designed to target both EGFR and MET signaling in tumors driven by specific molecular abnormalities. The U.S. Food and Drug Administration granted accelerated approval in May 2021 for adults with locally advanced or metastatic non-small cell lung cancer with activating EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. FDA subsequently approved amivantamab in combination with carboplatin and pemetrexed in March 2024 for first-line treatment of advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. In August 2024, FDA approved amivantamab in combination with lazertinib for first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations. In October 2025, FDA expanded amivantamab with carboplatin and pemetrexed to patients with EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease progressed after treatment with an EGFR tyrosine kinase inhibitor. In December 2025, FDA approved amivantamab combined with hyaluronidase for subcutaneous administration across the approved indications of intravenous amivantamab. In the European Union, Rybrevant received conditional marketing authorisation on 9 December 2021 and was converted to a standard marketing authorisation on 27 June 2024, with subsequent extensions covering additional EGFR-mutated NSCLC settings. Indian CDSCO records document approval of amivantamab for EGFR exon 20 insertion-positive NSCLC following progression on or after platinum-based chemotherapy. Key clinical programmes include CHRYSALIS, PAPILLON, MARIPOSA, MARIPOSA-2 and PALOMA.

Amivantamab is used for selected adults with advanced or metastatic non-small cell lung cancer whose tumors contain specific EGFR alterations. For EGFR exon 20 insertion-mutated NSCLC, amivantamab may be used as monotherapy after progression on or after platinum-based chemotherapy and, in applicable regulatory settings, in combination with carboplatin and pemetrexed as first-line treatment. For EGFR exon 19 deletion or exon 21 L858R substitution-mutated NSCLC, amivantamab is used in combination with lazertinib as first-line treatment in applicable indications. It is also used with carboplatin and pemetrexed for patients with these EGFR mutations whose disease has progressed following prior EGFR tyrosine kinase inhibitor treatment, according to the approved regulatory indication. The exact eligible population varies between jurisdictions. Treatment selection should be based on molecular testing, disease stage, previous systemic therapy, EGFR mutation type, performance status and the approved indication applicable to the specific product and country.

Amivantamab is administered according to the specific indication, formulation and patient body weight. Intravenous treatment uses weight-based dosing, with the first dose generally divided over two consecutive days, followed by weekly administration during the initial treatment period and then less frequent administration according to the approved regimen. In combination with carboplatin and pemetrexed, amivantamab is subsequently administered according to the defined treatment cycle, while regimens containing lazertinib generally use a two-week administration interval after the initial dosing period. The subcutaneous amivantamab and hyaluronidase formulation is administered according to its approved fixed-dose regimen and requires administration by a healthcare professional. Antihistamines, antipyretics and corticosteroids are used before specified early infusions to reduce infusion-related reactions, with premedication requirements depending on the formulation and regimen. Treatment is generally continued until disease progression or unacceptable toxicity. Dose interruption, delay or permanent discontinuation may be required for clinically significant adverse reactions.

Common side effects of amivantamab include infusion-related reactions, rash, nail disorders, swelling or edema, fatigue, muscle or joint pain, nausea, constipation, decreased appetite and changes in laboratory values. Skin-related effects can include acneiform rash, dry skin, itching and inflammation around the nails. When amivantamab is combined with carboplatin and pemetrexed, adverse effects may also include neutropenia, thrombocytopenia, anemia, vomiting, decreased appetite, low albumin and electrolyte abnormalities associated with the combination. Amivantamab with lazertinib may also be associated with additional risks such as venous thromboembolic events and treatment-related skin or laboratory abnormalities. The frequency and severity of adverse reactions vary according to the indication, combination therapy, formulation and individual patient characteristics. Many non-serious adverse effects can be managed with supportive care, monitoring and treatment modification under medical supervision.

Important serious risks associated with amivantamab include infusion-related reactions, interstitial lung disease or pneumonitis, venous thromboembolic events, severe skin reactions, eye-related adverse effects and clinically significant edema. Infusion reactions are particularly important during initial treatment and may include fever, chills, flushing, shortness of breath, nausea, chest discomfort or changes in blood pressure. Patients receiving amivantamab with lazertinib require particular attention to venous thromboembolism, and prophylactic anticoagulation is recommended in applicable treatment regimens. Interstitial lung disease or pneumonitis can present with new or worsening cough, shortness of breath or fever and requires prompt evaluation. Amivantamab can cause severe skin and nail reactions and may affect the eyes, including keratitis or other ocular complications. Treatment may need to be interrupted or permanently discontinued depending on the severity of toxicity. Amivantamab can cause fetal harm, and appropriate pregnancy precautions are required.

Before starting amivantamab, healthcare professionals should confirm the tumor's EGFR mutation status using an appropriate validated molecular diagnostic test and assess disease stage, prior treatment and relevant organ function. Baseline assessment should include respiratory status, skin and nail condition, ocular history, cardiovascular and thrombotic risk and laboratory parameters appropriate to the planned combination regimen. Patients should be monitored closely during initial administration for infusion-related reactions and should receive the recommended premedication. Patients receiving amivantamab with lazertinib require assessment and management of venous thromboembolic risk according to the approved regimen. New respiratory symptoms should be evaluated promptly for possible interstitial lung disease or pneumonitis. Patients should be advised regarding skin care and should report significant rash, nail inflammation or eye symptoms promptly. Conventional CYP-mediated drug interactions are generally less prominent for amivantamab itself because it is a monoclonal antibody, although combination partners such as lazertinib and chemotherapy have their own interaction and safety considerations. Concomitant medicines should therefore be reviewed before treatment.

Prescribers should confirm the precise EGFR mutation, disease setting, previous EGFR-targeted treatment and applicable regulatory indication before initiating amivantamab. Baseline assessment should include respiratory status, skin and nail examination, ocular history, thromboembolic risk and laboratory investigations appropriate to the planned regimen. Premedication requirements and the initial split-dose administration schedule should be verified carefully before the first infusion. Patients should be counselled to report breathing difficulty, new cough, fever, severe rash, painful or inflamed nails, eye pain or visual changes, leg swelling, chest pain or sudden shortness of breath promptly. Pharmacists should verify the formulation, weight-based or fixed-dose requirements, administration route, infusion or injection schedule and combination medicines. When amivantamab is combined with lazertinib, venous thromboembolism prevention and monitoring should be incorporated into treatment planning. Coordination between oncology, pharmacy, nursing, laboratory and ophthalmology teams can help identify and manage treatment-related toxicities early.