Merck RORs into phase 3

Merck & Co has been relatively quiet about zilovertamab vedotin, the ROR1-targeting ADC it gained through the $2.8bn acquisition of VelosBio in 2020. But hot on the heels of promising data in first-line DLBCL disclosed in an ASH abstract, the company is starting a pivotal trial in this setting, according to a new listing on clinicaltrials.gov. Similarly to the phase 2 Waveline-007 trial that will feature at ASH on Sunday, the phase 3 study, known as Waveline-010, will combine zilo-V with R-CHP chemotherapy. Unlike the uncontrolled phase 2, Waveline-010 will test this regimen against R-CHOP chemo, with a primary endpoint of progression-free survival. In Waveline-010 patients will receive zilo-V at 1.75mg/kg – this dose produced an 100% complete response rate among 15 patients in Waveline-007, according to the ASH abstract, while higher doses were linked with higher toxicity and lower response rates. Still, toxicity will be something to keep an eye on as, even in Waveline-007’s 1.75mg/kg cohort, 40% of patients experienced grade 3-4 adverse events. Perhaps because of this, that trial is also now evaluating a 1.5mg/kg dose. If Merck can find a therapeutic window it will buck the trend in ROR1, where various other groups have foundered.

Late-stage trials of zilovertamab vedotin

Source: OncologyPipeline & clinicaltrials.gov.