PR Newswire·Dec 10, 2025, 8:00 AM ET

Kazia Therapeutics Highlights New Clinical and Translational Findings Demonstrating Paxalisib's Ability to Reinvigorate Anti-Tumor Immunity Across Multiple Advanced Breast Cancer Populations including TNBC and HER2+

KZIA

Kazia Therapeutics presented new data at the 2025 San Antonio Breast Cancer Symposium regarding paxalisib, a brain-penetrant dual PI3K/mTOR inhibitor, showing activity in HER2-positive metastatic breast cancer & triple-negative breast cancer (TNBC).
In HER2+ disease ex-vivo studies, paxalisib reduced single circulating tumor cells (CTCs) by 42% & CTC clusters by 78%, including large clusters (≥5 cells) associated with metastatic progression.
Paxalisib disrupted aggressive mesenchymal CTC clusters marked by Vimentin⁺/Snail⁺/NRF2⁺ phenotypes & activated cytotoxic, interferon, & inflammatory pathways to reverse T-cell exhaustion in HER2+ patients.
The first patient in the TNBC PaxPlus-ABC Phase 1b trial (paxalisib + pembrolizumab + chemotherapy) demonstrated 76% tumor volume shrinkage & significant reductions in CTCs & clusters after one treatment cycle.
In the TNBC patient, temporary interruption of paxalisib led to a rapid resurgence of CTC clusters, whereas resumption restored suppression, indicating paxalisib is necessary to control these drivers unlike pembrolizumab alone.
Preliminary data indicates paxalisib facilitates epigenetic reprogramming of CTCs toward less aggressive phenotypes & revitalizes cytotoxic CD8 T-cell populations in TNBC.
Across both subtypes, pembrolizumab monotherapy failed to meaningfully reduce CTC burden, while paxalisib directly targets mesenchymal, metastatic, & epigenetically resistant CTC clusters.
Kazia suggests paxalisib offers a unifying therapeutic opportunity across HER2+, TNBC, & BRCA-mutated breast cancer subtypes by disrupting shared resistance mechanisms involving CTC clusters & immune exhaustion.