A pilot Phase 1 trial evaluating Oncternal Therapeutic’s investigational therapy cirmtuzumab as an add-on to standard chemotherapy for patients with advanced, HER2-negative breast cancer who cannot receive surgery has started dosing participants.
Cirmtuzumab is a human monoclonal antibody designed to bind to the receptor-tyrosine-kinase like orphan receptor 1 (ROR1), a protein located at the surface of breast cancer cells.
Tumor cells that express ROR1 have a higher potential to divide and contribute to tumor growth and spread. By binding to ROR1, cirmtuzumab blocks signals that promote cancer cell survival.
“Expression of ROR1 on primary breast cancers has been shown to be associated with a higher risk of relapse over time, and is correlated with markers of EMT (epithelial-mesenchymal transition). Treatment of breast cancer cells in the laboratory with cirmtuzumab, which binds with high affinity to cell-surface ROR1, inhibits tumor growth and metastasis,” James Breitmeyer, MD, PhD, Oncternal’s president and CEO, said in a press release.
The Phase 1b study (NCT02776917), ongoing at the University of California, San Diego and currently recruiting participants, is an open-label, non-randomized, fixed-dose study. Its primary goal is to determine the safety and tolerability of the combination therapy.
Patients will receive cirmtuzumab, administered into the blood at a dose of 600 milligrams (mg) every 14 days — on days 1 and 15 — for up to six cycles. The chemotherapy Taxol (paclitaxel) also will be delivered into the blood via weekly infusions. Treatment will be given for six months. Taxol may continue to be administered after cirmtuzumab is stopped.
Besides assessing the combination’s safety and tolerability, researchers will also evaluate the number of patients with complete and partial tumour responses, and those who achieve stable disease. Time to disease progression and levels of cirmtuzumab’s target protein, ROR1, will also be assessed.
Previous studies with animals showed that breast cancer cells treated with cirmtuzumab failed to form new tumors.
“In further preclinical studies, our collaborators showed that no tumors formed when cells harvested from breast cancer tumors treated with cirmtuzumab and paclitaxel were implanted into new animals,” Breitmeyer said. “These data validate the rationale for combining cirmtuzumab with paclitaxel, and Oncternal is excited to support the combination trial at UC San Diego.”
Cirmtuzumab was developed by researchers at the Moores Cancer Center using funding by the California Institute for Regenerative Medicine (CIRM) before Oncternal acquired the license to further develop it.
Cirmtuzumab is also being evaluated as a potential treatment for chronic lymphocytic leukemia and mantle cell lymphoma.