Zolbetuximab

UK SPC (Vyloy 100 mg powder for concentrate for solution for infusion, https://www.medicines.org.uk/emc/product/15889/smpc). Indication: locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction adenocarcinoma whose tumours are CLDN18.2 positive (defined as >=75% of tumour cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining on a validated test), given in combination with fluoropyrimidine- and platinum-containing chemotherapy. Cycle duration is determined by the chemotherapy backbone; the 400 mg/m2 every-2-weeks maintenance dose is based on a pharmacokinetic modelling exercise. Treatment should be initiated and supervised by a physician experienced in the use of anticancer therapies. PREMEDICATION: before each infusion, premedicate with a combination of antiemetics (e.g. NK-1 receptor blockers and/or 5-HT3 receptor blockers, plus other medicinal products as indicated) to prevent nausea and vomiting; if the patient has nausea and/or vomiting before administration, symptoms should be resolved to Grade <=1 before the first infusion. If given on the same day as fluoropyrimidine- and platinum-containing chemotherapy, zolbetuximab must be administered FIRST. INFUSION RATES (SPC Table 3) - start each infusion at a slower rate than the calculated rate and increase as tolerated after 30-60 minutes if no adverse reactions: loading 800 mg/m2 - 100 mg/m2/hr for the first 30-60 minutes then 200-400 mg/m2/hr; maintenance 600 mg/m2 every 3 weeks - 75 mg/m2/hr then 150-300 mg/m2/hr; maintenance 400 mg/m2 every 2 weeks - 50 mg/m2/hr then 100-200 mg/m2/hr. If the infusion time exceeds 8 hours from end of preparation, discard the bag and prepare a new one. DOSE MODIFICATION: no dose reduction is recommended - adverse reactions are managed by infusion rate reduction, interruption and/or discontinuation. Anaphylactic reaction, suspected anaphylaxis or Grade 3-4 hypersensitivity or infusion-related reaction: stop the infusion immediately and permanently discontinue. Grade 2 hypersensitivity or infusion-related reaction, Grade 2-3 nausea, or Grade 2-3 vomiting: interrupt until Grade <=1 then resume at a reduced rate for the remainder, and premedicate/use the Table 3 rates for the next infusion. Grade 4 vomiting: permanently discontinue. Elderly: no dose adjustment in patients >=65 years. Hepatic impairment: no dose adjustment in mild impairment; evaluated in only a limited number of patients with moderate impairment and not evaluated in severe impairment. PAEDIATRIC: safety and efficacy in the paediatric population have not been established (UK SPC); US labelling states safety and effectiveness in paediatric patients have not been established. Any under-18 use must be verified against a children's formulary and specialist paediatric oncology protocol. No interactions section (SPC 4.5) was retrieved in the source bundle - the clinician should check interactions against the full SPC.