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New ROR1-Targeting Antibody-Drug Conjugate Under Study in Treatment of Lymphoid Cancers

By: Vanessa A. Carter, BS
Posted: Friday, March 18, 2022

Michael L. Wang, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues evaluated the use of zilovertamab vedotin—an antibody-drug conjugate targeting receptor tyrosine kinase–like orphan receptor 1 (ROR1)—in patients with lymphoid cancers. These investigators discovered that this agent demonstrated antitumor activity in patients who were heavily pretreated, and the results of this trial were published in NEJM Evidence.

“Our findings provide clinical equipoise to support the further development of zilovertamab vedotin as monotherapy and combination therapy in patients with monomethyl auristatin E [MMAE]-sensitive hematological and solid tumors,” the study authors stated. “Importantly, our data provide validation of ROR1 as a therapeutic target, supporting the concept that selective targeting of ROR1 may offer a novel and clinically beneficial approach to cancer therapy if these data can be extended in larger and longer clinical trials.”

This phase I dose-escalation study enrolled 32 patients with previously treated mantle cell lymphoma (n = 15), chronic lymphocytic leukemia (n = 7), diffuse large B-cell lymphoma (DLBCL; n = 5), follicular lymphoma (n = 3), marginal zone lymphoma (n = 1), or Richter transformation lymphoma (n = 1). Participants received 0.5, 1.0, 1.5, 2.25, and 2.5  mg/kg of zilovertamab vedotin every 3 weeks until disease progression or unacceptable toxicity.

Zilovertamab vedotin targeting ROR1 on circulating tumor cells was documented in pharmacodynamic and pharmacokinetic data. Adverse events such as acute neutropenia and cumulative neuropathy occurred but were expected with an MMAE-containing antibody-drug conjugate; no adverse events were clinically concerning, noted the authors.

The recommended dose of zilovertamab vedotin was determined to be 2.5 mg/kg every 3 weeks. Objective tumor responses induced by zilovertamab vedotin were recorded in seven patients with mantle cell lymphoma, with four partial and three complete responses; three patients with DLBCL demonstrated response, with one partial and two complete responses. Interestingly, objective tumor responses were not detected among individuals with other tumor types.

Disclosure: For full disclosures of the study authors, visit evidence.nejm.org.


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