{"entity":{"id":"zilovertamab-vedotin","kind":"drug","name":"Zilovertamab vedotin","aka":[],"tldr":"Zilovertamab vedotin is a ROR1-directed ADC in phase 3 for large B-cell lymphoma.","summary":"Zilovertamab vedotin is an anti-ROR1 antibody carrying the microtubule inhibitor MMAE through a cleavable linker; ROR1 is an oncofetal receptor re-expressed on B-cell cancers including large B-cell lymphoma and largely absent from normal adult tissue, which makes it an attractive ADC address. Merck acquired the programme through VelosBio and is developing it chiefly in large B-cell lymphoma. The waveLINE-003 phase 3 trial combines it at 1.75 mg/kg every 3 weeks with rituximab, gemcitabine and oxaliplatin (R-GemOx) in relapsed DLBCL, and it is also being tested in first line. Neutropenia, peripheral neuropathy and fatigue are the expected MMAE-class toxicities. Whether ROR1 targeting adds to existing CD19- and CD20-directed options, including CAR-T and bispecifics, is the question phase 3 must answer. It is an ADC against a fetal-type receptor that lymphoma cells switch back on.","status":"phase-3","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov: trials of Zilovertamab vedotin","url":"https://clinicaltrials.gov/search?intr=MK-2140"}],"tags":[],"related":[],"cancers":["dlbcl"],"sections":[],"technologies":["adc"],"targets":["ror1"],"drugs":[],"companies":["merck"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06717347","nct05458297","nct06395103","nct05562830","nct05406401","nct06890884"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"MK-2140","modality":"ADC","payload":"MMAE","linker":"Cleavable","mechanism":"Anti-ROR1 with MMAE.","approvals":[],"mechanismSteps":["Antibody binds ROR1 on the tumour cell surface","Receptor-ADC complex is internalised by endocytosis","Trafficked to the lysosome; linker is cleaved or antibody degraded","MMAE is released inside the cell","Microtubule assembly is blocked; mitosis arrests","Tumour cell dies by apoptosis","Membrane-permeable payload diffuses to kill neighbouring antigen-negative cells (bystander effect)"],"dosing":{"route":"IV infusion","schedule":"Phase 3 dose 1.75 mg/kg every 3 weeks with R-GemOx","source":"https://clinicaltrials.gov/study/NCT05139017"},"toxicity":[{"event":"Neutropenia"},{"event":"Peripheral neuropathy"},{"event":"Fatigue"}],"access":[{"country":"US","reimbursement":"Investigational","asOf":"2026-09-06"}],"regulatoryEvents":[]},"route":"/drugs/zilovertamab-vedotin/","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":"ror1","kind":"target","name":"ROR1","route":"/targets/ror1/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"trial":[{"id":"nct06890884","kind":"trial","name":"A Clinical Study of Zilovertamab Vedotin (MK-2140) Plus Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Polatuzumab Vedotin Plus R-CHP in People With Diffuse Large B-cell Lymphoma (DLBCL) (MK-2140-011/waveLINE-011)","route":"/trials/nct06890884/"},{"id":"nct05458297","kind":"trial","name":"A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-","route":"/trials/nct05458297/"},{"id":"nct05406401","kind":"trial","name":"A Study of Zilovertamab Vedotin (MK-2140) in Combination With Cyclophosphamide, Doxorubicin, and Prednisone Plus Rituximab or Rituximab Biosimilar (Truxima) (R-CHP) in Participants With Diffuse Large B-Cell Lymphoma (DLBCL) (MK-2140-007)","route":"/trials/nct05406401/"},{"id":"nct06717347","kind":"trial","name":"A Study to Evaluate Zilovertamab Vedotin (MK-2140) Combination With Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituxi","route":"/trials/nct06717347/"},{"id":"nct05562830","kind":"trial","name":"A Substudy of Investigational Agents in Programmed Cell Death-1/Ligand 1 (PD-1/L1) Refractory Locally Advanced or Metastatic Urothelial Carcinoma (mUC) (MK-3475-04A)","route":"/trials/nct05562830/"},{"id":"nct06395103","kind":"trial","name":"Substudy 01A: Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)","route":"/trials/nct06395103/"},{"id":"waveline-003","kind":"trial","name":"waveLINE-003","route":"/trials/waveline-003/"}],"term":[{"id":"mmae","kind":"term","name":"MMAE","route":"/terms/mmae/"},{"id":"tubulin-inhibitor-payloads","kind":"term","name":"Tubulin inhibitor payloads","route":"/terms/tubulin-inhibitor-payloads/"}],"institution":[{"id":"ucsd-moores","kind":"institution","name":"UC San Diego Moores Cancer Center","route":"/institutions/ucsd-moores/"}]}}