# Zilovertamab vedotin

Source: https://onco.cc/drugs/zilovertamab-vedotin/  
OnCo record `zilovertamab-vedotin` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Treatment
- Status: phase-3
- Last checked: 2026-09-04
- Code: MK-2140
- Modality: ADC
- Mechanism: Anti-ROR1 with MMAE.
- Payload: MMAE
- Linker: Cleavable
- Dosing: IV infusion; Phase 3 dose 1.75 mg/kg every 3 weeks with R-GemOx

## Sources

- ClinicalTrials.gov: trials of Zilovertamab vedotin: https://clinicaltrials.gov/search?intr=MK-2140

## Connected records

- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- targets: [ROR1](https://onco.cc/targets/ror1/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- trials: [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)](https://onco.cc/trials/nct06890884/), [A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-](https://onco.cc/trials/nct05458297/), [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)](https://onco.cc/trials/nct05406401/), [A Study to Evaluate Zilovertamab Vedotin (MK-2140) Combination With Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituxi](https://onco.cc/trials/nct06717347/), [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)](https://onco.cc/trials/nct05562830/), [Substudy 01A: Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)](https://onco.cc/trials/nct06395103/), [waveLINE-003](https://onco.cc/trials/waveline-003/)
- terms: [MMAE](https://onco.cc/terms/mmae/), [Tubulin inhibitor payloads](https://onco.cc/terms/tubulin-inhibitor-payloads/)
- institutions: [UC San Diego Moores Cancer Center](https://onco.cc/institutions/ucsd-moores/)

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