demcizumab + pemetrexed

**Demcizumab + pemetrexed** is an investigational combination therapy that includes demcizumab, a humanized monoclonal antibody targeting Delta-like ligand 4 (DLL4), and pemetrexed, a standard antineoplastic chemotherapy agent (folate antimetabolite) used for various cancers. Demcizumab inhibits DLL4-mediated Notch signaling, impacting cancer stem cell maintenance and tumor vasculature. Pemetrexed inhibits folate-dependent metabolic processes, critical for cell replication. This combination was primarily investigated for first-line treatment of metastatic non-squamous non-small cell lung cancer (NSCLC), usually in combination with carboplatin. Demcizumab was developed by OncoMed Pharmaceuticals; Alimta (pemetrexed) is developed and marketed by Eli Lilly. Trials of this combination revealed promising anti-tumor activity initially but also demonstrated significant cardiopulmonary toxicities with continuous demcizumab dosing and ultimately did not show a benefit in Phase 2 clinical trials. Further development has been discontinued[2][3][5][7][8].