amivantamab

Overview

Amivantamab is a therapeutic bispecific antibody used in oncology, with activity directed against epidermal growth factor receptor (EGFR) and MET-proto-oncogene (MET). It is described in the recent literature as an EGFR-MET bispecific antibody with immune cell-directing activity, reflecting a mechanism that combines receptor targeting with immune-mediated antitumor effects. In clinical practice, it has been positioned as a treatment for non-small cell lung cancer (NSCLC), particularly in tumors with EGFR exon 20 insertion mutations.

Biologically, amivantamab is significant because it targets two pathways implicated in tumor growth and resistance: EGFR signaling and MET signaling. This dual targeting is relevant in EGFR-mutated NSCLC, where resistance mechanisms can involve MET-related bypass signaling. Its development and use have therefore been closely associated with combination strategies, including chemotherapy and carboplatin-pemetrexed, as well as with studies evaluating its role relative to other emerging approaches such as antibody-drug conjugate-based strategies.

Focus of Latest Publications

Recent publications on amivantamab have focused primarily on its role in EGFR-mutated non-small cell lung cancer, especially tumors with EGFR exon 20 insertion mutations. In the phase 3 PAPILLON program, amivantamab combined with carboplatin-pemetrexed was evaluated as first-line treatment for previously untreated locally advanced or metastatic NSCLC with EGFR exon 20 insertions, and the global trial had already shown a significant progression-free survival benefit over chemotherapy alone. The Asia subgroup analysis extended this work by examining clinical outcomes in Asian participants. Another publication highlighted updated CHRYSALIS-2 data suggesting that amivantamab plus lazertinib may be a new option for patients with atypical EGFR mutations, with early efficacy associated with durable overall survival.

Several recent papers also addressed how amivantamab is being integrated into broader treatment strategies and dosing approaches. One study described the development of a weight-tiered every-3-weeks regimen of amivantamab with carboplatin-pemetrexed, using population pharmacokinetics and exposure-response analyses to support the switch from every 2 weeks to every 3 weeks. The analysis found comparable trough concentrations between the new and approved regimens, a flat exposure-response relationship for progression-free survival after adjustment for covariates, and a generally manageable safety profile, supporting registration of the revised regimen in the new indications.

Real-world evidence is also emerging. The Italian ATLAS Registry study examined amivantamab in advanced NSCLC with EGFR exon 20 insertion mutations, reflecting its growing use as a standard-of-care option in this population and addressing the need for safety and efficacy data outside clinical trials. In parallel, a review of antibody-drug conjugates in EGFR-mutant NSCLC with acquired resistance to third-generation EGFR tyrosine kinase inhibitors noted chemotherapy plus amivantamab among novel combination strategies under discussion for overcoming resistance. Another early-phase study, OrigAMI-1, investigated amivantamab monotherapy in chemorefractory RAS/BRAF wild-type metastatic colorectal cancer, underscoring interest in extending its EGFR-MET-directed activity beyond lung cancer, although the abstract provided only the study context and rationale.

Key Publications

Jul Rare EGFRm NSCLC: More First-Line Options Emerge. (Cancer discovery, 2026, PMID 42224429): "Meanwhile, updated CHRYSALIS-2 data point to amivantamab combined with lazertinib as a new option for patients with atypical EGFR mutations, with initial efficacy translating to durable overall survival."
Jun Amivantamab in advanced non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations: Real-world data from the Italian ATLAS Registry. (Cancer, 2026, PMID 42216441): "The bispecific antibody amivantamab is the new standard of care for this population but real-world safety and efficacy data are lacking."
Jun Development of the Weight-Tiered Q3W Regimen of Amivantamab in Combination With Carboplatin-Pemetrexed in EGFR-Mutated Non-Small Cell Lung Cancer. (CPT: pharmacometrics & systems pharmacology, 2026, PMID 42166539): "Amivantamab, a bispecific antibody targeting epidermal growth factor and mesenchymal-epithelial transition receptors, was initially approved under accelerated approval as a monotherapy for second-line treatment of non-small cell lung cancer (NSCLC) with exon 20 insertion mutations."
Jun Amivantamab Monotherapy in Chemorefractory RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study. (Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2026, PMID 42013403): "Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, is approved in non-small cell lung cancer (NSCLC)."
Apr The emerging role of antibody-drug conjugates in EGFR-mutant non-small cell lung cancer with acquired resistance to third-generation EGFR tyrosine kinase inhibitors. (Journal of controlled release : official journal of the Controlled Release Society, 2026, PMID 41730505): "...including novel combination strategies such as chemotherapy plus amivantamab or ivonescimab."
Apr Amivantamab plus chemotherapy versus chemotherapy for first-line treatment of participants with EGFR exon 20 insertion-mutated advanced non-small cell lung cancer: PAPILLON Asia subgroup analysis. (Lung cancer (Amsterdam, Netherlands), 2026, PMID 41671628): "Amivantamab is a bispecific, epidermal growth factor receptor (EGFR) and MET-proto-oncogene (MET)-targeting antibody with immune cell-directing activity."