{"entity":{"id":"zolbetuximab","kind":"drug","name":"Zolbetuximab","aka":[],"tldr":"Zolbetuximab is the first drug against Claudin 18.2, a protein exposed on stomach cancer cells. Added to chemotherapy it extends survival by two to three months; nausea is the price.","summary":"Chimeric IgG1 binding CLDN18.2, killing via ADCC and CDC. SPOTLIGHT and GLOW positive; FDA approval 18 October 2024 with a companion IHC assay (VENTANA CLDN18). Eligible patients are CLDN18.2 ≥75% moderate-to-strong membranous staining, HER2-negative. Nausea and vomiting occur in most patients in cycle 1 and need aggressive antiemetic prophylaxis and infusion-rate adjustment.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Zolbetuximab","links":[{"label":"FDA label","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761365s000lbl.pdf"}],"tags":[],"related":["cldn18-2-expression"],"cancers":["gastric","gastric-cldn18-2-positive","oesophageal-adenocarcinoma"],"sections":[],"technologies":["monoclonal-antibody","companion-diagnostic"],"targets":["cldn18-2"],"drugs":[],"companies":["astellas"],"institutions":[],"pathways":[],"terms":["adcc"],"trials":["spotlight-glow","nct06901531","nct03816163","nct03505320","nct07431281"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Vyloy","code":"IMAB362","modality":"Monoclonal antibody (anti-Claudin 18.2)","mechanism":"Binds CLDN18.2 exposed on malignant gastric cells; Fc-mediated ADCC and complement-dependent cytotoxicity.","approvals":[{"region":"Japan","year":2024,"indication":"CLDN18.2+ HER2- gastric cancer (first approval, March 2024)"},{"region":"US","year":2024,"indication":"First-line CLDN18.2+ (≥75%), HER2- locally advanced/metastatic gastric or GEJ adenocarcinoma with fluoropyrimidine/platinum chemotherapy"},{"region":"EU","year":2024,"indication":"1L CLDN18.2+ HER2- gastric/GEJ; 19 Sep 2024"}],"mechanismSteps":["Normal stomach cells hide Claudin 18.2 inside tight junctions; cancer cells expose it on their surface","Zolbetuximab binds the exposed protein","Its IgG1 tail recruits NK cells (ADCC) and complement (CDC)","The coated tumour cells are killed; some normal gastric mucosa is hit too, causing nausea"],"dosing":{"route":"Intravenous","schedule":"800 mg/m² loading, then 600 mg/m² every 3 weeks or 400 mg/m² every 2 weeks with chemotherapy","modifications":"Slow or interrupt infusion for nausea/vomiting; premedicate with antiemetics","monitoring":"Nausea/vomiting in cycle 1; hypersensitivity","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761365s000lbl.pdf"},"toxicity":[{"event":"Nausea","note":"Most patients; worst in cycle 1"},{"event":"Vomiting","note":"Most patients; infusion-related"},{"event":"Decreased appetite"},{"event":"Hypersensitivity/infusion reactions"}],"access":[],"regulatoryEvents":[{"date":"2024-03","type":"approval","region":"Japan","note":"World-first approval"},{"date":"2024-10-18","type":"approval","region":"US","note":"SPOTLIGHT/GLOW; companion diagnostic VENTANA CLDN18 (43-14A)"}]},"route":"/drugs/zolbetuximab/","neighbours":{"biomarker":[{"id":"cldn18-2-expression","kind":"biomarker","name":"Claudin 18.2 expression (>= 75% of tumour cells, moderate to strong)","route":"/biomarkers/cldn18-2-expression/"}],"cancer":[{"id":"gastric-cldn18-2-positive","kind":"cancer","name":"Claudin 18.2-positive gastric cancer","route":"/cancers/gastric-cldn18-2-positive/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"oesophageal-adenocarcinoma","kind":"cancer","name":"Oesophageal and junctional adenocarcinoma","route":"/cancers/oesophageal-adenocarcinoma/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"gastric-pdl1-high","kind":"cancer","name":"PD-L1-high gastric cancer","route":"/cancers/gastric-pdl1-high/"}],"technology":[{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"target":[{"id":"cldn18-2","kind":"target","name":"Claudin 18.2","route":"/targets/cldn18-2/"}],"company":[{"id":"astellas","kind":"company","name":"Astellas","route":"/companies/astellas/"}],"term":[{"id":"adcc","kind":"term","name":"ADCC (antibody-dependent cellular cytotoxicity)","route":"/terms/adcc/"}],"trial":[{"id":"nct03505320","kind":"trial","name":"A Study of Zolbetuximab (IMAB362) in Adults With Gastric Cancer","route":"/trials/nct03505320/"},{"id":"nct03816163","kind":"trial","name":"A Study of Zolbetuximab (IMAB362) in Adults With Pancreatic Cancer","route":"/trials/nct03816163/"},{"id":"nct06901531","kind":"trial","name":"A Study of Zolbetuximab Together With Pembrolizumab and Chemotherapy in Adults With Gastric Cancer","route":"/trials/nct06901531/"},{"id":"nct07431281","kind":"trial","name":"Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2","route":"/trials/nct07431281/"},{"id":"spotlight-glow","kind":"trial","name":"SPOTLIGHT & GLOW","route":"/trials/spotlight-glow/"}],"pairing":[{"id":"cldn18-antibody-then-adc","kind":"pairing","name":"CLDN18.2 antibody first line → CLDN18.2 ADC or CAR-T on progression","route":"/pairings/cldn18-antibody-then-adc/"}],"idea":[{"id":"idea-biomarker-quadruplet-gastric","kind":"idea","name":"Biomarker-directed first-line quadruplets in gastric cancer","route":"/ideas/idea-biomarker-quadruplet-gastric/"}],"person":[{"id":"lee-jeeyun","kind":"person","name":"Jeeyun Lee","route":"/people/lee-jeeyun/"},{"id":"shitara-kohei","kind":"person","name":"Kohei Shitara","route":"/people/shitara-kohei/"},{"id":"ryu-min-hee","kind":"person","name":"Min-Hee Ryu","route":"/people/ryu-min-hee/"},{"id":"rha-sun-young","kind":"person","name":"Sun Young Rha","route":"/people/rha-sun-young/"},{"id":"kang-yoon-koo","kind":"person","name":"Yoon-Koo Kang","route":"/people/kang-yoon-koo/"}],"paper":[{"id":"paper-glow-zolbetuximab-nat-med-2023","kind":"paper","name":"GLOW: zolbetuximab plus CAPOX in claudin 18.2-positive, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma","route":"/key-papers/paper-glow-zolbetuximab-nat-med-2023/"}],"pathway":[{"id":"gastric-cancer-signalling","kind":"pathway","name":"Gastric cancer (KEGG map)","route":"/pathways/gastric-cancer-signalling/"}]}}