FDA agrees to design and major details of ZILO-301, a phase III study of zilovertamab in R/R MCL

On January 4, 2022, following a successful end-of-phase II meeting, it was announced that the U.S. Food and Drug Administration (FDA) has agreed to the design and key elements of ZILO-301, a phase III trial of zilovertamab plus ibrutinib in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL).¹ Based on this input from the FDA, the clinical trial protocol and statistical analysis plan for ZILO-301 is being finalized.¹

Interim results from the phase Ib/II study of zilovertamab (formerly cirmtuzumab) plus ibrutinib in patients with R/R MCL and R/R or treatment-naïve chronic lymphocytic leukemia (CLL) were presented during a poster session at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition on December 13, 2021.^2,3 Zilovertamab 600 mg every 2 weeks for three cycles and then every 4 weeks in combination with ibrutinib starting on Day 0 was selected as the recommended dose following the dose-escalation portion of the study.³ As of the data cutoff date, median progression-free survival and duration of response were not reached in the MCL cohort, which is still enrolling patients in the dose-expansion phase of the trial.³ No dose-limiting toxicities or serious treatment-related adverse events were attributed to zilovertamab alone.²

Zilovertamab is a first-in-class, investigational monoclonal antibody targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1).² ROR1 is an onco-embryonic antigen that, when expressed by cancer cells, promotes their growth and survival.^2,3 As it is not typically expressed by noncancerous cells in adults, it is an attractive therapeutic target. Zilovertamab has been shown to inhibit the proliferation, migration, and survival of tumor cells that express ROR1, and it has also been shown to work synergistically with the Bruton’s tyrosine kinase inhibitor ibrutinib.^2,3

The phase III ZILO-301 study will be an international, multicenter study with at least 50 participating centers that have expertise in treating MCL. The trial is expected to begin enrolling patients in the second quarter of 2022.¹