Trial Work Progressing and Encouraging for Zilovertamab Vedotin Combo in DLBCL

The WaveLINE-003 phase 2/3 clinical trial is an evaluation of combining the novel ROR1-targeting antibody-drug conjugate zilovertamab vedotin (ZV) with rituximab plus gemcitabine-oxaliplatin (R-GemOx) to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Results from the dose confirmation stage of this trial were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, Illinois.

“Zilovertamab vedotin in combination with R-GemOx demonstrated promising efficacy and acceptable safety in R/R [relapsed or refractory] DLBCL at the RP2D [recommended phase 2 dose] of ZV of 1.75 mg/kg plus R-GemOx,” wrote investigators led by Philippe Armand, MD, PhD, of Dana-Farber Cancer Institute, Boston, Massachusetts, presenting their findings at the Meeting.

This stage enrolled 40 adult patients with relapsed or refractory DLBCL who had undergone at least one line of therapy. These patients were also ineligible for chimeric antigen receptor (CAR) T-cell therapy and autologous stem-cell transplant (ASCT), or these treatments were unsuccessful. In the total cohort, 55% of enrollees were aged 65 years or older, 18% had received prior CAR T-cell therapy, 18% had received prior ASCT, and the median number of prior lines of therapy was 2.0.

All 40 patients received ZV plus R-GemOx, administered once every three weeks for at least six cycles. ZV was dosed at 1.5 mg/kg in 17 patients, at 1.75 mg/kg in 16 patients, and 2.0 mg/kg in seven patients. Respectively in these ZV dosing subgroups, one, two, and four patients reported dose-limiting toxicities.

Over a median follow-up of 9.8 months in the cohort, the recommended phase 2 dose was determined to be 1.75 mg/kg.

In the 1.5 mg/kg, 1.75 mg/kg, and 2.0 mg/kg ZV dosing subgroups, the objective response rate was 27%, 56%, and 57%, respectively. The median duration of response in the three subgroups was 14.4 months, 8.7 months, and not reached, respectively. The median overall survival (OS) was 11.5 months, not reached, and 7.4 months, respectively, and the rate of 6-month OS was 70.0%, 78.8%, and 68.6%, respectively.

Thirty-nine patients in the total cohort experienced at least one treatment-related adverse event (TRAE). The most prevalent TRAEs in the total cohort were diarrhea, nausea, anemia, and platelet count decrease, at 45%, 38%, 28%, and 28% respectively. 65% of the total cohort reported grade 3 or worse severity TRAEs, the most prevalent of which were neutropenia, neutrophil count decrease, platelet count decrease, and anemia, at 23%, 23%, 23%, and 20%, respectively.

There were two patients in the 2.0 mg/kg ZV dosing subgroup who discontinued the treatment regimen due to a TRAE; one had sepsis which led to mortality, and the other had respiratory failure.

Randomization of patients has begun for phase 3 of the WaveLINE-003 trial, which will involve a comparison of ZV plus R-GemOx against R-GemOx.