{"entity":{"id":"zynlonta","kind":"drug","name":"Loncastuximab tesirine","aka":[],"tldr":"Loncastuximab tesirine (Zynlonta) is a CD19 ADC with a DNA-crosslinking payload for relapsed large B-cell lymphoma.","summary":"Loncastuximab tesirine (Zynlonta) is a humanised anti-CD19 antibody carrying SG3199, a pyrrolobenzodiazepine (PBD) dimer that forms interstrand DNA crosslinks, through a cleavable valine-alanine linker at a drug-to-antibody ratio of about 2.3. It is given at 0.15 mg/kg every 3 weeks for two cycles, then 0.075 mg/kg, with dexamethasone premedication, for relapsed or refractory DLBCL after two or more lines. Accelerated approval in 2021 rested on LOTIS-2 (objective response rate 48 percent), and the EU granted conditional authorisation in 2022. PBD payloads are extremely potent but bring oedema and effusions, photosensitivity, thrombocytopenia and raised GGT, toxicities that have limited the class in solid tumours. Its place alongside CD19 CAR-T and CD20 bispecifics remains to be settled. It is a CD19-directed ADC with a DNA-crosslinking payload for lymphoma that has come back.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Loncastuximab_tesirine","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Loncastuximab%20tesirine"}],"tags":[],"related":[],"cancers":["dlbcl"],"sections":[],"technologies":["adc"],"targets":["cd19"],"drugs":[],"companies":["adc-therapeutics"],"institutions":[],"pathways":[],"terms":["val-ala"],"trials":["nct04384484","nct05658562"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Zynlonta","modality":"ADC","payload":"SG3199 (PBD dimer, DNA crosslinker), DAR ~2.3","linker":"Val-Ala, cleavable","mechanism":"Humanised anti-CD19 with PBD dimer; interstrand DNA crosslinks.","approvals":[{"region":"US","year":2021,"indication":"Relapsed/refractory DLBCL after ≥2 systemic therapies"},{"region":"EU","year":2022,"indication":"R/R DLBCL ≥2 lines (conditional)"}],"mechanismSteps":["Antibody binds CD19 on the tumour cell surface","Receptor-ADC complex is internalised by endocytosis","Trafficked to the lysosome; linker is cleaved or antibody degraded","SG3199 (PBD dimer) is released inside the cell","DNA is damaged (crosslinks or double-strand breaks)","Tumour cell dies by apoptosis","Membrane-permeable payload diffuses to kill neighbouring antigen-negative cells (bystander effect)"],"dosing":{"route":"IV infusion","schedule":"0.15 mg/kg every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks; dexamethasone premedication","modifications":"Hold for grade ≥3 oedema/effusion or cytopenias","monitoring":"Weight and fluid status, blood counts, LFTs, photosensitivity precautions","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Thrombocytopenia"},{"event":"Increased GGT"},{"event":"Neutropenia"},{"event":"Anaemia"},{"event":"Fatigue"},{"event":"Oedema and effusions"},{"event":"Photosensitivity/rash"}],"access":[{"country":"US","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2021-04-23","type":"accelerated-approval","region":"US","note":"Accelerated approval, relapsed/refractory DLBCL after ≥2 lines (LOTIS-2) The confirmatory requirement was still open 5.4 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"Treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma."},{"date":"2022-12","type":"approval","region":"EU","note":"Conditional marketing authorisation","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/zynlonta/","neighbours":{"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"}],"company":[{"id":"adc-therapeutics","kind":"company","name":"ADC Therapeutics","route":"/companies/adc-therapeutics/"}],"term":[{"id":"pbd-dimer-payloads","kind":"term","name":"DNA crosslinker payloads (PBD dimers)","route":"/terms/pbd-dimer-payloads/"},{"id":"pbd-sg3199","kind":"term","name":"PBD dimer (SG3199 / tesirine)","route":"/terms/pbd-sg3199/"},{"id":"val-ala","kind":"term","name":"Val-Ala dipeptide","route":"/terms/val-ala/"},{"id":"lymphoma-tx-uk-access","kind":"term","name":"What the NHS in England funds for lymphoma, appraisal by appraisal","route":"/terms/lymphoma-tx-uk-access/"}],"trial":[{"id":"nct05658562","kind":"trial","name":"A Study of MT-2111 in Patients With Relapsed/Refractory DLBCL","route":"/trials/nct05658562/"},{"id":"lotis-2","kind":"trial","name":"LOTIS-2","route":"/trials/lotis-2/"},{"id":"nct04384484","kind":"trial","name":"Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lym","route":"/trials/nct04384484/"}],"biomarker":[{"id":"cd19-expression","kind":"biomarker","name":"CD19 expression (CD19-positive)","route":"/biomarkers/cd19-expression/"}]}}