Johnson & Johnson Submits IND Application in China for Subcutaneous Formulation of EGFR/c-Met Bispecific Antibody Amivantamab

On June 21, the CDE website showed that Johnson & Johnson's bispecific antibody amivantamab, targeting EGFR and c-Met, had been submitted for clinical trial in China in a subcutaneous injection formulation. As early as July 2020, Johnson & Johnson/Janssen had already applied to the CDE for the intravenous injection formulation of amivantamab, and in September of the same year, it was granted breakthrough therapy designation by the CDE.

Amivantamab is a bispecific antibody that targets EGFR resistance mutations, MET mutations, and amplifications. It can simultaneously bind to the extracellular structures of EGFR and c-Met, block the binding of ligands to EGFR and MET, promote receptor degradation, and trigger antibody-dependent cellular cytotoxicity.

On May 21, 2021, the FDA granted accelerated approval to amivantamab intravenous injection (brand name: Rybrevant) based on the Phase I clinical data submitted by Johnson & Johnson/Janssen on December 4, 2020. The drug is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease has progressed after platinum-based chemotherapy. This was the first FDA-approved drug targeting this specific mutation at that time. Johnson & Johnson submitted a marketing application to the EMA on December 28, 2020, and received approval from the EMA on December 10, 2021.

According to the structure disclosed in previous literature, the amivantamab bispecific antibody adopts a 1+1 asymmetric format (IgG1), with one Fab of the antibody binding to the cMet target and the other Fab binding to the EGFR target.

EGFR (Epidermal Growth Factor Receptor) is a glycoprotein that belongs to the tyrosine kinase-type receptor family. It traverses the cell membrane with a molecular weight of 170 kDa and is widely distributed on the surface of mammalian epithelial cells, fibroblasts, glial cells, keratinocytes, and other cell types. The EGFR signaling pathway plays a crucial role in physiological processes such as cell growth, proliferation, and differentiation.

c-Met (c-Mesenchymal-epithelial transition factor) is a member of the receptor tyrosine kinase family. The mature cMET molecule consists of an extracellular α chain with a molecular weight of 50 kDa and a transmembrane β chain of 140 kDa, playing a crucial role in cell proliferation, survival, invasion, tissue development, and organ regeneration. Overexpression of c-Met occurs in various types of solid tumors, including brain tumors, breast cancer, colorectal cancer, gastric cancer, head and neck cancer, lung cancer, liver cancer, skin cancer, prostate cancer, and soft tissue sarcomas.

Nextpharma of PharmaCube shows that currently, there are 6 EGFR/c-Met bispecific antibody drugs with disclosed R&D progress globally. Companies in China developing EGFR/c-Met bispecific antibody drugs include EpimAb Biotherapeutics and Betta Pharmaceuticals. Genor Biopharma has laid out GB263T, the world's first EGFR/cMET/cMET trispecific antibody.

It is worth mentioning that the formulation of Johnson & Johnson's EGFR/c-Met bispecific antibody submitted for clinical trials this time is subcutaneous injection. Compared with intravenous injection, subcutaneous injection can significantly improve the convenience of medication, enhance the quality of life for cancer patients, reduce the risk of infection in patients requiring central venous catheter infusion, and lower the cost of receiving medical services.

Clinicaltrials.gov disclosed in October 2020 a Phase I clinical study (NCT04606381, PALOMA study) on the subcutaneous injection formulation of amivantamab for the treatment of advanced solid malignant tumors. The Phase I results of the PALOMA study presented at this year’s AACR conference showed that the use of the subcutaneous injection formulation of amivantamab demonstrated excellent efficacy and safety.

Reference: A Novel Bispecific Antibody Targeting EGFR and cMet is Effective Against EGFR Inhibitor Resistant Lung Tumors.