KEY TAKEAWAYS
- The phase 1b trial aimed to assess zilovertamab and paclitaxel safety in advanced breast cancer patients, focusing on tolerability.
- The study concluded that the combination was safe and well tolerated in heavily pre-treated advanced breast cancer patients. Further research is needed.
Zilovertamab, a humanized monoclonal antibody, targets ROR1, an onco-embryonic antigen present in various solid tumors like breast cancer. Previous phase 1 research demonstrated its efficacy in inhibiting ROR1 signaling pathways, including ERK1/2, NF-κB, and NRF2 activation.
Rebecca A. Shatsky and her team conducted a study that aimed to investigatethe safety and tolerability of combining zilovertamab with paclitaxel in advanced breast cancer patients.
The study included patients with locally advanced, unresectable, or metastatic HER2-negative breast cancer, ECOG performance status 0-2, and no prior taxane therapy in the advanced setting. Treatment comprised intravenous administration of 600 mg zilovertamab on Days 1 and 15 of Cycle 1, followed by Day 1 of each 28-day cycle, alongside weekly paclitaxel at 80 mg/m2.
The findings revealed that participants in the study had a median history of four prior therapies (a combination of endocrine therapy and chemotherapy) for locally advanced, unresectable, or metastatic disease.
No patients ceased treatment due to zilovertamab-related toxicity. Adverse events were consistent with paclitaxel’s known safety profile. Of 16 patients, 6 (38%) achieved a partial response, and 6 out of 16 (38%) patients maintained stable disease as their best tumor response.
The study concluded that the combination of zilovertamab and paclitaxel demonstrated safety and good tolerability among heavily pre-treated advanced breast cancer patients. Further assessment of ROR1 targeting with zilovertamab in breast cancer patients is warranted.
Funding support was provided by Oncternal Therapeutics, Inc., Pedal the Cause at UC San Diego Moores Cancer Center, the Gonick Breast Cancer Research Fund, and the Breast Cancer Personalized Treatment Research Fund, the California Institute for Regenerative Medicine (CIRM) UC San Diego Alpha Clinic, the National Cancer Institute (NCI), Curebound, the Sanford Stem Cell Institute, and the April Krueger Women’s Health Initiative.
Source: https://pubmed.ncbi.nlm.nih.gov/38408999/
Clinical Trial: https://clinicaltrials.gov/study/NCT02776917
Shatsky, R.A., Batra-Sharma, H., Helsten, T., et al. (2024). “A phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic Her2-negative breast cancer.” Breast Cancer Res 26, 32 (2024). https://doi.org/10.1186/s13058-024-01782-0.
