Merck Advances Middle Dose of ROR1 ADC in Relapsed/Refractory DLBCL After Safety Review

Merck is advancing the 1.75 mg/kg (middle dose) of its ROR1-directed antibody-drug conjugate (ADC), zilovertamab vedotin, in clinical trials for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after balancing efficacy and safety concerns.24

The decision follows dose-ranging studies where higher doses led to more discontinuations and severe adverse events, including grade 3–4 toxicities and a fatal case of sepsis at the 2.0 mg/kg dose.24

At 1.75 mg/kg, the ADC demonstrated strong anti-tumor activity, including complete response rates, while maintaining a more manageable safety profile:
63% of patients had grade ≥3 adverse events (primarily neutropenia, anemia, and thrombocytopenia), but these were mostly manageable, with no treatment-related deaths reported.24

The discontinuation rate from adverse events was lower at the middle dose:
in one cohort, 8 of 16 patients completed treatment; most discontinuations were due to disease progression rather than toxicity.2

Merck is running phase 3 trials of zilovertamab vedotin in both previously untreated and relapsed/refractory DLBCL (including the global waveLINE-003 and waveLINE-010 studies), aiming to establish it as a frontline and salvage therapy option.24

The asset, acquired via Merck’s $2.75 billion purchase of VelosBio, is positioned as a potentially safer, effective alternative to other ADCs such as polatuzumab vedotin, particularly for patients who have failed prior therapies.24

Sources:

2. https://www.fiercebiotech.com/biotech/merck-plays-lion-tamer-taking-middle-dose-ror-adc-forward-amid-adverse-events

4. https://www.ainvest.com/news/zilovertamab-vedotin-merck-gen-adc-poised-dominate-relapsed-refractory-dlbcl-markets-2506/