Zolbetuximab (IMAB-362)

Mechanism of action

From the NCI Drug Dictionary: A chimeric immunoglobulin G1 (IgG1) monoclonal antibody directed against the tumor-associated antigen (TAA) Claudin18.2 (CLDN18.2; A2 isoform of claudin-18), with potential immunostimulating and antineoplastic activities. Upon administration, zolbetuximab specifically targets and binds to CLDN18.2 expressed on tumor cells. This may kill CLDN18.2-expressing tumor cells by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and inhibit cell proliferation.

Preliminary data

Gastric cancer

1. SPOTLIGHT: Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, Van Cutsem E, Xu RH, Aprile G, Xu J, Chao J, Pazo-Cid R, Kang YK, Yang J, Moran D, Bhattacharya P, Arozullah A, Park JW, Oh M, Ajani JA. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023 May 20;401(10389):1655-1668. Epub 2023 Apr 15. Erratum in: Lancet. 2023 Jul 22;402(10398):290. link to original article PubMed NCT03504397
2. GLOW_gastric: Shah MA, Shitara K, Ajani JA, Bang YJ, Enzinger P, Ilson D, Lordick F, Van Cutsem E, Gallego Plazas J, Huang J, Shen L, Oh SC, Sunpaweravong P, Soo Hoo HF, Turk HM, Oh M, Park JW, Moran D, Bhattacharya P, Arozullah A, Xu RH. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023 Aug;29(8):2133-2141. Epub 2023 Jul 31. link to original article link to PMC article PubMed NCT03653507

Also known as

• Code names: GC-182, IMAB-362