Paxalisib Trial Expands to HR-Positive, HER2-Negative Breast Cancer

Kazia Therapeutics is expanding its breast cancer trial of paxalisib to include patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR-positive/HER2-negative) advanced breast cancer. The move is based on early laboratory findings that the drug may help tumors respond again to treatments they have stopped responding to.

Paxalisib is an investigational oral pill, taken once daily, that blocks the PI3K/mTOR pathway. Kazia first developed it for glioblastoma, a type of brain cancer, and has tested it in more than 550 patients with the disease. A breast cancer researcher later approached the company about testing the drug in breast cancer. That work led to an ongoing trial in triple-negative breast cancer.

HR-positive/HER2-negative disease makes up 60% to 70% of all breast cancers, according to Dr. John Friend, CEO of Kazia Therapeutics. Hormone therapy and CDK4/6 inhibitors are the foundation of treatment for advanced disease. Many patients stop responding to these drugs over time, however, and their cancer continues to grow.

"In our preclinical models with [paxalisib]… it appeared to be able to resensitize these tumors such that these CDK4/6 inhibitors could then become effective again," Friend explained.

Friend noted that these findings come from laboratory and animal models. "They help us understand biology, they help us generate hypotheses," he said. He added that such data cannot guarantee the same effect in patients.

The new trial arm will enroll patients whose metastatic disease progressed after first-line treatment. It will test two dose levels of paxalisib combined with Faslodex (fulvestrant) and Ibrance (palbociclib), compared with standard treatment. The primary goal is to show that paxalisib is safe in this combination. Researchers will also study blood and tissue samples to look for biomarkers that could identify which patients respond best.

The trial is enrolling only in Australia for now. "It is our intention to rapidly expand the ongoing trial into other … countries," Friend said. He added that expanding into the U.S. is a near-term priority.

Kazia has submitted abstracts to the San Antonio Breast Cancer Symposium in December. Friend expects peer-reviewed publication in 2027.

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