Dr. Lee on Potential Challenges With VLS-101 in MCL and DLBCL

Hun Ju Lee, MD, an assistant professor of medicine in the Department of Lymphoma and Myeloma, and the Jessica and Jeffrey Brue Endowed Professor of Lymphoma Research at The University of Texas MD Anderson Cancer Center, discusses potential challenges with VLS-101 in mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL).

VLS-101 is an investigational antibody-drug conjugate (ADC) that targets ROR1, an oncofetal protein that can be pathologically re-expressed after birth in hematologic and solid tumors. During the 2020 ASH Annual Meeting and Exposition, findings from a first-in-human phase 1 trial evaluating VLS-101 were presented virtually and demonstrated proof-of-concept for targeting ROR1 in patients with heavily pretreated advanced MCL or DLBCL.

The activity of VLS-101 doesn’t appear to be as significant as that observed with cirmtuzumab, a ROR1-directed monoclonal antibody, says Lee. However, this could be because VLS-101 utilizes a cytotoxic chemotherapy payload that can be difficult to tolerate for some patients. For example, in Hodgkin lymphoma, similar challenges have been faced with brentuximab vedotin (Adcetris). The naked antibody of brentuximab vedotin did not confer clinical benefit to patients; however, the ADC, which utilizes a monomethyl auristatin E cytotoxic agent, has shown efficacy, but with the drawback of potential peripheral neuropathy, Lee says. Ultimately, additional investigation into ROR1-targeted agents, including CAR T-cell therapies, is needed in the lymphoma space, concludes Lee.