100% Response in Phase II Lymphoma Trial

At a pre-planned analysis, zilovertamab vedotin in combination with R-CHP achieved a 100% (n=15) complete response (CR) rate in patients treated with zilovertamab vedotin at 1.75 mg/kg. Based on the data, the study has established 1.75 mg/kg as the recommended Phase III dose of zilovertamab vedotin. These data were in an oral presentation (Abstract #578) at ASH.

“There is a need for additional first-line treatment options to help patients with diffuse large B-cell lymphoma, since, unfortunately, approximately 40% still experience relapsed or refractory disease after initial treatment with the current standard of care,” said Dr. Muhit Ozcan, the study’s principal investigator, Ankara University School of Medicine. “These data from the Phase II waveLINE-007 trial are promising and support further research in the first-line setting in a larger patient population to help address this significant unmet need for patients.”

“We are pleased to see these early positive results from the Phase II waveLINE-007 trial, in which zilovertamab vedotin demonstrated a highly promising response rate and a manageable safety profile in combination with standard of care,” said Dr. Gregory Lubiniecki, vice president, oncology clinical research, Merck Research Laboratories. “We look forward to advancing our research of this investigational ROR1-directed antibody drug conjugate, which we believe has strong potential in multiple hematologic malignancies.”

Study design and additional data from waveLINE-007

WaveLINE-007 is a non-randomized, open-label Phase II trial (ClinicalTrials.gov, NCT05406401 ) evaluating zilovertamab vedotin (MK 2140) in combination with R CHP in patients with previously untreated DLBCL. The primary endpoints are safety (number of patients with dose limiting toxicity, adverse events and discontinuation due to adverse events) and CR rate based on investigator review per Lugano Response Criteria. Secondary endpoints include objective response rate (ORR) and duration of response (DOR) per Lugano Response Criteria. As of data cut-off, 36 patients were enrolled in the study to receive zilovertamab vedotin plus R CHP intravenously on day 1 of each 21-day cycle (Q3W) for up to eight cycles. The treatment arms of the study included:

i) 1.75 mg/kg (n=15); all 15 patients in this arm completed the trial (none discontinued).

ii) 2.0 mg/kg (n=15); 14 patients in this arm completed treatment and one patient discontinued after cycle 1 due to physician decision and was entered to safety follow-up, or

iii) 2.25 mg/kg (n=6); 5 patients in this arm completed treatment and one patient discontinued due to physician decision.

The efficacy results showed a CR was achieved in combination with R-CHP in 100% (n=15) of patients receiving the 1.75 mg/kg dose of zilovertamab vedotin (CI: 95%, 78.2-100.0), 93.3% (n=14) of patients receiving the 2.0 mg/kg dose (CI: 95%, 68.1-99.8) and 100% (n=6) of patients receiving the 2.25 mg/kg dose (CI: 95%, 54.1-100.0). The total CR rate at the end of treatment was 97.2% (CI: 95%, 85.5-99.9). The median follow-up for all patients was 17.6 months (range, 7.1-24.6). The ORR was 100% (CI: 95%, 78.2-100.0) for patients receiving the 1.75 mg/kg dose, 93.3% (CI: 95%, 68.1-99.8) for patients receiving the 2.0 mg/kg dose, and 100% (CI: 95%, 54.1-100.0) for patients receiving the 2.25 mg/kg dose, all in combination with R-CHP. The median DOR has not been reached for all patients, and the total 12-month DOR was 93.5%. Based on the data, the recommended zilovertamab vedotin dose was determined to be 1.75 mg/kg.

Serious treatment-related adverse events (TRAEs) occurred in 11% (n=4) of all patients (1.75 mg/kg [n=1], 2.0 mg/kg [n=1], 2.25 mg/kg [n=2]). Grade 3-4 TRAEs occurred in 58% (n=21) of all patients. The most common of these events were neutropenia, nausea, anemia and diarrhea.