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amivantamab + pemetrexed

Development stage: Unknown
Lead developer: Janssen Research & Development
Modality: Bispecific Antibodies → Multispecific Antibodies → Engineered Antibody Formats → Antibody-Based Therapeutics, Small Molecules
Administration: Intravenous, Intrathecal

Overview

Amivantamab + pemetrexed is an investigational combination therapy consisting of the bispecific antibody amivantamab and the antifolate chemotherapy agent pemetrexed. Amivantamab targets both the epidermal growth factor receptor (EGFR) and the mesenchymal-epithelial transition (MET) receptor, inhibiting ligand binding and receptor dimerization to disrupt tumor growth signaling. Pemetrexed is a small molecule that inhibits multiple folate-dependent enzymes, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), thereby blocking nucleotide synthesis. This combination is primarily being evaluated for the treatment of leptomeningeal metastasis arising from EGFR-mutated non-small cell lung cancer (NSCLC), utilizing a novel administration strategy where pemetrexed is delivered both systemically and intrathecally to overcome the blood-brain barrier.

Other names: amivantamab plus pemetrexed

Targets

MET (Mesenchymal-epithelial transition factor receptor)TS (Thymidylate synthase)FCGR3A (Low affinity immunoglobulin gamma Fc region receptor III-A)DHFR (Dihydrofolate reductase)GART (GAR transformylase)EGFR T790M (Epidermal growth factor receptor T790M mutant)

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