1.75-Dose New Drug Achieves 100% Remission in Lymphoma

On December 8, Merck announced the preliminary results of its Phase II waveLINE-007 study for the first time. This study aimed to evaluate the efficacy and safety of the antibody-drug conjugate (ADC) zilovertamab vedotin, targeting the receptor tyrosine kinase-like orphan receptor 1 (ROR1), in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for treatment-naive patients with diffuse large B-cell lymphoma (DLBCL). The results showed that in the patient group receiving a dose of 1.75 mg/kg of zilovertamab vedotin (n=15), the complete remission rate (CR) reached 100%. These data were presented in an oral report at the 66th Annual Meeting of the American Society of Hematology (ASH) and were assigned abstract number #578.

Merck acquired VelosBio for $2.75 billion in November 2020, gaining its ROR1 ADC drug, zilovertamab vedotin (VLS-101), which was then in early clinical development and had received orphan drug designation (ODD) and fast track designation (FTD) from the U.S. Food and Drug Administration (FDA) for the treatment of mantle cell lymphoma (MCL).

The waveLINE-007 study is an open-label Phase II clinical trial (NCT05406401) that enrolled 36 treatment-naive DLBCL patients, divided into three treatment groups based on the dosage of zilovertamab vedotin (1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg). The primary endpoints were safety assessment and complete remission rate (CR), with secondary endpoints including objective response rate (ORR) and duration of remission (DOR).

Efficacy results indicated that the complete remission rates for the three different dosage groups of zilovertamab vedotin were 100% (n=15), 93.3% (n=14), and 100% (n=6), leading to an overall complete remission rate of 97.2%. However, one patient in each of the 2.0 mg/kg and 2.25 mg/kg dosage groups discontinued treatment due to adverse events, confirming the optimal dosage as 1.75 mg/kg.

Regarding safety, the incidence of serious treatment-related adverse events (TRAE) was 11% (n=4), while the incidence of grade 3-4 TRAEs was 58% (n=21). The most common adverse events included neutropenia, nausea, anemia, and diarrhea.

Dr. Muhit Ozcan, the principal investigator from Ankara University Medical School, noted, “Despite initial treatment, about 40% of DLBCL patients still experience poor efficacy or disease relapse, highlighting the urgent need for additional first-line treatment options for these patients. The data from the waveLINE-007 study is very promising and supports further clinical studies in larger patient populations to address unmet clinical needs.”

Dr. Gregory Lubiniecki, Vice President of Oncology Clinical Research at Merck Research Laboratories, expressed, “We are very pleased with the early positive results from the Phase II waveLINE-007 study, especially with the high response rate and manageable safety profile of zilovertamab vedotin when used in combination with standard therapies. We look forward to advancing research on ADC drugs targeting ROR1, believing it holds great potential in various hematological malignancies.”