On December 8, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the first presentation of data from the Phase 2 waveLINE-007 trial evaluating zilovertamab vedotin, Merck’s investigational antibody drug conjugate (ADC) that targets receptor tyrosine kinase-like orphan receptor 1 (ROR1), in combination with cyclophosphamide, doxorubicin and prednisone plus rituximab (R-CHP) for the treatment of patients with previously untreated diffuse large B-cell lymphoma (DLBCL) (Press release, Merck & Co, DEC 8, 2024, View Source [SID1234648868]). 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 3 dose of zilovertamab vedotin. These data are being presented for the first time today in an oral presentation (Abstract #578) at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 2 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 2 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."

As announced, data from more than 20 abstracts are being presented from across a broad range of hematologic malignancies from Merck’s hematology pipeline, which includes a diverse range of investigational assets with novel modalities, at the 66th ASH (Free ASH Whitepaper) Annual Meeting and Exposition.

Study design and additional data from waveLINE-007

WaveLINE-007 is a non-randomized, open-label Phase 2 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:

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

About diffuse large B-cell lymphoma

Lymphoma is cancer beginning in the lymphatic system – the network of organs, vessels and tissues that protects the body from infection. There are many subtypes of lymphoma, which are often categorized into two main types – Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). DLBCL, the most common form of NHL, is derived from white blood cells that grow rapidly and uncontrollably, enlarging the lymph nodes and often migrating to other parts of the body. DLBCL accounts for approximately 25-30% of all non-Hodgkin lymphomas worldwide. In the U.S., it is estimated that approximately 25,000 patients are diagnosed with DLBCL each year. The five-year relative survival rate for DLBCL is 60-70%.

About zilovertamab vedotin (MK-2140)

Zilovertamab vedotin is an investigational ADC that targets ROR1. ROR1 is a transmembrane protein that is overexpressed in multiple hematologic malignancies. Merck is committed to research with zilovertamab vedotin across B-cell malignancies and is establishing a robust program of clinical trials under the name waveLINE. The waveLINE program includes a Phase 2/3 study in patients with relapsed or refractory DLBCL (waveLINE-003, NCT05139017) and a Phase 3 study in treatment naïve patients with DLBCL (waveLINE-010, NCT06717347).