Merck (NYSE: MRK), known as MSD outside the United States and Canada, has presented promising results from its Phase 2 waveLINE-007 trial at the 66th American Society of Hematology (ASH) Annual Meeting. The trial evaluated zilovertamab vedotin, an investigational antibody-drug conjugate (ADC) targeting ROR1, in combination with cyclophosphamide, doxorubicin, prednisone, and rituximab (R-CHP) for treating patients with previously untreated diffuse large B-cell lymphoma (DLBCL). At a pre-planned analysis, the combination therapy achieved a 100% complete response (CR) rate in patients treated with zilovertamab vedotin at a dose of 1.75 mg/kg. Based on these results, 1.75 mg/kg has been established as the recommended Phase 3 dose for further studies.
Dr. Muhit Ozcan, the study’s principal investigator from Ankara University School of Medicine, emphasized the need for new first-line treatment options for DLBCL, as around 40% of patients relapse or experience refractory disease after standard treatments. He stated, “These data are promising and support further research in a larger population to address this significant unmet need.”
Dr. Gregory Lubiniecki, Vice President of Oncology Clinical Research at Merck Research Laboratories, expressed enthusiasm about the results, noting that zilovertamab vedotin demonstrated a promising response rate and manageable safety profile. Merck is excited to advance its research on this ROR1-targeted ADC, which has potential in treating multiple hematologic malignancies.
WaveLINE-007 is a non-randomized, open-label Phase 2 trial assessing the efficacy and safety of zilovertamab vedotin combined with R-CHP in 36 previously untreated DLBCL patients. The study aimed to evaluate the complete response (CR) rate, safety, objective response rate (ORR), and duration of response (DOR). The treatment was administered intravenously every 21 days for up to eight cycles, with the following dosing arms:
- 1.75 mg/kg (15 patients): 100% CR rate
- 2.0 mg/kg (15 patients): 93.3% CR rate
- 2.25 mg/kg (6 patients): 100% CR rate
The total CR rate at the end of treatment was 97.2%. The ORR was 100% for the 1.75 mg/kg and 2.25 mg/kg groups, and 93.3% for the 2.0 mg/kg group. Notably, the median DOR had not yet been reached, but the 12-month DOR was 93.5%. Serious treatment-related adverse events (TRAEs) occurred in 11% of patients, with the most common being neutropenia, nausea, anemia, and diarrhea.
Zilovertamab vedotin targets ROR1, a protein overexpressed in several hematologic malignancies, and is being tested across multiple studies, including the waveLINE-003 and waveLINE-010 trials, which investigate its use in relapsed/refractory and treatment-naïve DLBCL patients, respectively.
Merck remains committed to advancing treatments for hematologic cancers and continues its leadership in oncology with a diverse pipeline of investigational medicines.
