A Phase 1b/2a Study of the ROR1-Targeting Monoclonal Antibody, Cirmtuzumab, and the Bruton Tyrosine Kinase Inhibitor, Ibrutinib, in B-Cell Cancers

Study CIRM-0001 entitled, “A Phase 1b-2 Study of the ROR1-Targeting Monoclonal Antibody, Cirmtuzumab (UC-961), and the Bruton Tyrosine Kinase Inhibitor, Ibrutinib, in Patients with B-Cell Lymphoid Malignancies”, also known as the CIRLL Trial (Cirmtuzumab plus Ibrutinib for Relapsed Leukemia and Lymphoma), is ongoing for long-term follow-up of patients. Enrollment is completed.  As of 02Feb2022, enrollment of patients with CLL and MCL is complete. Thirty-four CLL patients (Parts 1 & 2) have received combination treatment with zilovertamab and ibrutinib. Part 3 CLL dosed 18 zilovertamab/ibrutinib patients and 10 ibrutinib only patients. Twelve MCL patients have received combination treatment with zilovertamab and ibrutinib in Part 1, and 21 patients have been dosed in Part 2, for a total of 33 patients treated as of March 31, 2022.  An interim clinical data update was presented at the June 2022 ASCO meeting which evaluated the safety and efficacy of zilovertamab alone or in combination with ibrutinib in patients with MCL and CLL patients as of 08 APR 2022. The combination treatment of zilovertamab plus ibrutinib is generally well tolerated with a safety profile similar to that of historical ibrutinib alone.  In patients with MCL, grade 3 or 4 neutropenia occurred in only 9.1% of patients administered the combination, compared to a historical value of 29% for patients receiving ibrutinib alone in its registration study. In part 3 of the study 20% of the CLL pts had severe neutropenia in the ibrutinib alone arm and only 5% had severe neutropenia for CLL patients randomized to ibrutinib plus zilovertamab. At this interim analysis we observed prolonged PFS for treated patients with MCL or CLL who had TP53 mutations and/or were in high-risk subgroups.  We also observed high objective response rates and durable responses in heavily pre-treated patients with MCL who were treated with zilovertamab + ibrutinib.  The combination of zilovertamab plus ibrutinib has been well tolerated, with treatment emergent adverse events consistent with those reported for ibrutinib alone. There have been no dose-limiting toxicities and no serious adverse events attributed to zilovertamab alone.