Kazia Expands Trial of Paxalisib for Advanced Breast Cancer

Kazia Therapeutics is expanding a clinical trial to test paxalisib in patients with advanced hormone receptor (HR)-positive, HER2-negative breast cancer. The drug will be evaluated in combination with fulvestrant and palbociclib, focusing on safety and tolerability. This expansion builds on the company’s ongoing efforts to address treatment resistance in this patient population, which remains a significant clinical challenge.

This move follows preclinical research suggesting paxalisib may help tumors regain sensitivity to CDK4/6 inhibitors, a critical advancement for patients whose cancers have progressed despite prior therapies. The study aims to determine if these findings translate into clinical benefits, potentially offering a new treatment option for those with limited alternatives.

Addressing Treatment Resistance

Treatment resistance remains a significant challenge for patients with advanced HR-positive, HER2-negative breast cancer, especially after progression on endocrine therapy and CDK4/6 inhibitors. Despite the transformative impact of these treatments, resistance often develops, leading to disease progression and reduced treatment options. Dr. John Friend, CEO of Kazia Therapeutics, emphasized that while endocrine therapies and CDK4/6 inhibitors have improved outcomes, there is still a critical need for strategies to overcome resistance.

Preclinical Findings and Biomarker Research

That was an important finding for us because it suggested paxalisib may be doing more than inhibiting the PI3K/mTOR pathway. The drug’s unique ability to cross the blood-brain barrier and penetrate critical areas within cancer cells, such as the nucleus, further distinguishes it from other therapies. Investigators are studying blood and tumor tissue samples to identify biomarkers or mutations associated with response, which could help tailor treatment to patients most likely to benefit.

Trial Design and Objectives

The trial will evaluate two doses of paxalisib combined with fulvestrant and palbociclib, alongside a comparator arm receiving fulvestrant alone. This design will help determine if paxalisib adds clinical benefit, particularly in patients whose disease has progressed on prior therapies. Safety and tolerability are the primary objectives, given this is the first time paxalisib is being tested in this combination and patient population.

Paxalisib has already been studied in more than 550 patients across brain cancer programs, providing a foundation of safety and tolerability data. The study will also investigate whether the drug can resensitize tumors resistant to CDK4/6 inhibition, a key question for patients with limited treatment options.

Enrollment and Future Steps

Initially, the trial will enroll patients in Australia with metastatic HR-positive, HER2-negative breast cancer who have progressed after first-line therapy. These patients represent a population with high unmet need, as their cancers have become resistant to standard treatments. Plans are underway to expand the study to additional countries, including the United States, broadening access to this investigational therapy.