Tolerability of Zilovertamab and Ibrutinib in Phase 1/2 Trial of MCL

Hun Ju Lee, MD, associate professor of medicine in the Department of Lymphoma & Myeloma at The University of Texas MD Anderson Cancer Center, discusses safety results of the phase 1/2 study (NCT05431179) of zilovertamab plus ibrutinib (Imbruvica) for patients with mantle Cell Lymphoma (MCL), chronic lymphocytic leukemia (CLL), or marginal zone lymphoma (MZL).

Zilovertamab is a fully humanized monoclonal antibody that inhibits the signaling of the ROR1 onco-embryonic kinase-like receptor, which is expressed in CLL, MCL, and MZL. Preclinically studies showed the potential for zilovertamab to inhibit CLL cell expression of genes induced by activated NF-kB, ERK1/2, NRF2, and STAT3 pathways, which may promote the growth and survival of TP53-mutated CLL in those patients on Bruton’s tyrosine kinase inhibitor ibrutinib.

In this phase 1/2 study, researchers looked at the addition of zilovertamab to patients being treated with ibrutinib and found an overall response rate of 89.3% (n = 25) in patients with MCL and 91.2% (n = 31) in patients with CLL. Moreover, they looked at the safety of adding the monoclonal antibody and found that adverse events (AEs) did not significantly change from what was observed with the ibrutinib monotherapy.

Transcript:

0:08 | In terms of safety, obviously safety is a big concern for us for this regimen, as there's a brand-new antibody combined with ibrutinib. We're obviously very concerned about making sure that this is a safe regimen for our patient population. And what we saw, in summary, was that this was no significantly different than that of the ibrutinib single agent and we didn't know, atrial fibrillation, which was a special AE of interest was only in 9% [of patients], and neutropenic fever was only seen in 1% [of patients].

0:45 | So we were very pleased and optimistic about the combination being very well tolerated. Based on that backbone, we got into the efficacy data and in terms of MCL we saw a very robust response that was rapid and durable.