Oncternal Therapeutics (NASDAQ: ONCT) has released updated interim clinical data from its ongoing Phase 1/2 Study CIRM-0001.

The study is evaluating zilovertamab, an investigational anti-ROR1 monoclonal antibody, in combination with ibrutinib in patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL). The study is being conducted in collaboration with the University of California San Diego and has been partially funded by the California Institute for Regenerative Medicine (CIRM).

Oncternal says that updated data has shown that the combination of zilovertamab and ibrutinib provided a significant clinical benefit to patients with MCL and CLL. The rapid onset of deep responses in MCL patients has led to the initiation of a randomized global Phase 3 study (ZILO-301) to further evaluate the combination.

The response rates and prolonged progression-free survival seen in MCL and CLL patients expressing the p53 mutation/del(17p) were especially encouraging, as these patients are underserved by current standard of care treatments.

The data also showed that the objective response rate was 89% in evaluable MCL patients, with a complete response rate of 43% at 26 months and 18% at 3 months. These rates were significantly higher than those seen with single-agent ibrutinib, which had an objective response rate of 66%, a complete response rate of 20% and a median progression-free survival of 12.8 months.

In CLL patients, the company says that data shows that the combination of zilovertamab and ibrutinib provided a 100% landmark progression-free survival at 42 months in patients expressing the p53 mutation/del(17p), and a median progression-free survival of 33.4 months in all evaluable CLL patients.

These results suggest that the combination therapy may be effective in treating difficult-to-treat patients with high-risk factors.

Overall, the company says that the data provides further evidence of the potential of zilovertamab in combination with ibrutinib to provide significant clinical benefit to patients with hematological malignancies. The company will continue to evaluate the combination therapy in ongoing clinical studies.

The CIRM-0001 Study is a clinical trial that is looking at the effects of a combination of zilovertamab and ibrutinib in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL). The trial has completed enrollment for the dose-finding and dose-expansion cohorts in CLL and MCL, as well as the randomized Phase 2 cohort in CLL. An additional dose-expansion cohort for up to 10 patients with MZL has begun enrolling patients.

Zilovertamab is a monoclonal antibody under investigation for its ability to target the Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) protein. This protein is expressed on the surface of some cancer cells, but not on normal adult cells, making it an attractive target for cancer therapy. Zilovertamab has been shown to bind to ROR1 and block its signaling, which may inhibit the growth and spread of cancer cells.

Two investigator-sponsored studies are also being conducted at UC San Diego to evaluate the use of zilovertamab in the treatment of metastatic castration-resistant prostate cancer (mCRPC) and relapsed/refractory CLL in combination with venetoclax, a Bcl-2 inhibitor. The Food and Drug Administration has granted Orphan Drug Designations to zilovertamab for the treatment of MCL and CLL/small lymphocytic lymphoma.

Shares of Oncternal Therapeutics trade on the NASDAQ under the symbol ONCT. For more information visit www.oncternal.com.