A phase I/II study of the humanized monoclonal antibody zilovertamab and ibrutinib in relapsed or refractory (R/R) mantle cell lymphoma (MCL) showed that the combination was well-tolerated and had a similar safety profile when compared with ibrutinib alone.
The retrospective study, led by Hun Ju Lee, MD, of the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center, also investigated the combination in patients with chronic lymphocytic leukemia (CLL) and in those patients with CLL plus p53 mutations.
The results of the trial were presented during the 64th American Society of Hematology Annual Meeting and Exposition in New Orleans, Louisiana, in December 2022.
The trial enrolled patients with R/R MCL who received one or more prior lines of therapy or with treatment-naïve or R/R CLL who received one or more prior lines of therapy. There were three parts of the study: a dose-escalation portion, a dose-expansion portion, and a 2:1 randomization in only the CLL group to receive zilovertamab and ibrutinib versus ibrutinib alone.
In patients with R/R MCL, the objective response rate (ORR) was 85.2%, which included 40.7% complete response (CR) and 44.4% partial response, with a median duration of response of 34.1 months (95% CI, 13.67 to not estimated). The CR rate was 29.6%, 37.0%, and 40.7% at six, 12, and 26 months, respectively. The median progression-free survival (mPFS) was 35.9 months (95% CI, 17.3-NE).
With respect to grade ≥3 neutropenia in patients with R/R MCL, the rate observed with the combination of zilovertamab and ibrutinib was 9.1%, lower than the 29.0% previously reported for ibrutinib alone.
“In this study, [zilovertamab plus ibrutinib] is well-tolerated with a safety profile that is very similar compared with [ibrutinib] alone.
The most frequent (≥30%) treatment emergent adverse events, regardless of causality, for all patients (MCL and CLL) treated with the combination therapy (n=85), were fatigue (42.4%), contusion (36.5%), and diarrhea (37.6%).
The mPFS was not reached for all patients with CLL at a median follow-up of 32.9 months. However, for patients with CLL and p53 alterations, overall efficacy of the combination of zilovertamab and ibrutinib was very promising with a PFS at 30 months of 100% compared with a historic locoregional PFS of around 55% for ibrutinib monotherapy.
“For [patients with CLL] with p53 alterations, overall efficacy with zilovertamab and ibrutinib is also very promising,” the investigators wrote.
The trial began enrolling patients with R/R marginal zone lymphoma who received one or more prior anti-CD20-based treatments in June 2022.
Lee HJ, Choi MJ, Siddiqi T, et al. Phase 1/2 study of zilovertamab and ibrutinib in mantle celll (MCL), chronic lymphocytic leukemia (CLL), or marginal zone lymphoma (MZL). Abstract #232. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.