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simtuzumab + leucovorin + irinotecan + fluorouracil
- Development stage
- Unknown
- Lead developer
- Gilead Sciences
- Modality
- Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
- Administration
- Intravenous
01
Overview
Simtuzumab + leucovorin + irinotecan + fluorouracil is a combination therapy comprising **simtuzumab** (a humanized IgG4 monoclonal antibody), **leucovorin** (folinic acid), **irinotecan** (a topoisomerase I inhibitor), and **fluorouracil** (an antimetabolite). Simtuzumab specifically targets and inhibits lysyl oxidase-like 2 (LOXL2), thereby blocking extracellular matrix remodeling and desmoplastic reaction in tumors. The standard FOLFIRI (folinic acid/leucovorin, fluorouracil, irinotecan) backbone acts via inhibition of DNA synthesis (fluorouracil), stabilization of the fluorouracil effect (leucovorin), and inhibition of topoisomerase I (irinotecan), leading to DNA strand breaks. The combination was evaluated in metastatic KRAS-mutant colorectal carcinoma as second-line treatment, but the addition of simtuzumab to FOLFIRI did not improve clinical outcomes over FOLFIRI alone, though it maintained similar tolerability profiles[1][4].
- Other names
- FOLFIRI + simtuzumab
02
Targets
TOP1 (DNA Topoisomerase I)LOXL2 (Lysyl oxidase-like 2 protein)DHFR (Dihydrofolate reductase)TS (Thymidylate synthase)
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