Zilovertamab is an investigational monoclonal antibody designed to inhibit the function of Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1). Zilovertamab has been evaluated in Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with MCL, chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL). Zilovertamab is also being evaluated in two investigator-initiated studies: a Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, in patients with R/R CLL (NCT04501939), and a Phase 1b study of zilovertamab in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (NCT05156905).
In April 2023 we announced a strategic reprioritization based on the rapidly changing commercial landscape for Bruton’s tyrosine kinase inhibitors (BTK inhibitors), under which Phase 3 study ZILO-301 and Phase 1/2 study CIRM-001* of zilovertamab in combination with ibrutinib will be closed, in order to extend the company’s cash runway into 2025 and focus efforts upon the clinical development of ONCT-808 and ONCT-534.
The decision was not based on any concerns about the safety or efficacy of zilovertamab. We plan to continue exploring the potential value of zilovertamab in areas of high unmet medical need. The robust response rates and prolonged PFS seen for MCL and CLL patients expressing TP53 aberrations will be further investigated preclinically and extended into other tumor types, such as lung cancer and prostate cancer. We expect partnerships and collaborations to be essential for executing future late-stage clinical trials of zilovertamab.
*CIRM-0001 will allow enrolled patients to continue treatment until ~June 2024 under a very reduced protocol.