Kazia Therapeutics Expands Paxalisib Trial for HR+ Breast Cancer

Kazia Therapeutics, an oncology-focused biotechnology company, has expanded its clinical trial for paxalisib into hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer, following promising preclinical data. The expansion, which will evaluate paxalisib in combination with fulvestrant and palbociclib, aims to determine the drug’s efficacy and safety in this patient population.

According to Dr. John Friend, Chief Executive Officer of Kazia Therapeutics, HR+/HER2- breast cancer accounts for approximately 60 to 70% of all breast cancer diagnoses in the United States, with nearly 322,000 new cases expected this year. "This significant unmet medical need represents a substantial area where paxalisib may offer a transformative treatment option," Friend stated.

Preclinical data from Kazia Therapeutics indicate that paxalisib, when combined with standard-of-care therapy, is well-tolerated and produces statistically significant antitumor activity in HR+ breast cancer. Specifically, the drug has been shown to resensitize CDK4/6 inhibitor-resistant tumors to standard-of-care therapy. Based on these findings, the company has amended its ongoing TNBC (Triple-Negative Breast Cancer) trial to include an additional arm evaluating paxalisib in combination with fulvestrant and palbociclib.

"The expanded trial will compare the combination therapy of paxalisib with fulvestrant and palbociclib against standard-of-care treatment," explained Dr. Sudha Rao, Chief Scientific Officer of Kazia Therapeutics. "Our preclinical data show that paxalisib can resensitize treatment-resistant tumors through a distinct epigenetic mechanism, an effect not observed with gedatolisib, an FDA-approved intravenous PI3K/mTOR inhibitor."

Paxalisib, an investigational brain-penetrant inhibitor of the PI3K/Akt/mTOR pathway, has been the subject of over 15 clinical trials. The company has also filed a provisional patent application based on its preclinical findings, which include identifying a high-risk subset of metastatic HR+/HER2- breast cancer defined by a novel PI3K/mTOR biomarker. Extensive benchmarking studies have shown that paxalisib can resensitize treatment-resistant tumors to combination therapy, with primary tumor growth inhibition comparable to gedatolisib.

Kazia Therapeutics expects to enroll the first patient in the expanded trial by the end of 2026, with full enrollment anticipated by the end of 2027. The primary endpoint of the trial will be safety and tolerability, with progression-free survival, overall response rate, and overall survival as secondary endpoints.

"Given the completion of our recent financing, we now have the capital in place to fund this program through its completion," Friend added. "Our ongoing efforts to advance this promising drug candidate in HR+ breast cancer represent a significant step forward in the treatment of this challenging disease."

The company is also advancing other clinical-stage programs, including EVT801, a small molecule inhibitor of VEGFR3, and NDL2, a potentially first-in-class intracellular PD-L1 protein degrader program targeting a newly identified mechanism of immunotherapy resistance and metastatic progression. Both programs are currently in preclinical development.