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Kazia Therapeutics Shares Impactful Findings on Paxalisib

Kazia Therapeutics Limited recently made headlines at the 2025 San Antonio Breast Cancer Symposium (SABCS) by unveiling new insights into their investigational treatment, paxalisib. This innovative drug has been shown to significantly bolster the immune response in patients battling advanced breast cancer, specifically in populations with HER2-positive metastatic breast cancer and triple-negative breast cancer (TNBC).

Key Takeaways from Recent Data

The presentations highlighted not just the potential of paxalisib but also provided compelling mechanistic insights into how it operates within the body. Findings demonstrated that paxalisib can effectively disrupt the clusters of circulating tumor cells (CTCs), characterized as powerful drivers of metastatic disease. Through advanced liquid biopsy techniques, researchers tracked changes in CTC behavior, discovering that paxalisib has an impressive capability to diminish both solitary CTCs and their aggressive clusters.

Disruption of CTC Clusters

In the context of HER2-positive metastatic breast cancer, paxalisib's effectiveness was marked by a striking reduction in CTC populations. It was observed that patients, despite exhibiting radiographic responses to traditional HER2-directed therapies, still retained significant residual CTC clusters, which are known to facilitate metastasis. In ex vivo studies, researchers reported reductions of 42% in single CTCs and an astonishing 78% in CTC clusters, shedding light on paxalisib's disruptive qualities. These clusters exhibited a mesenchymal phenotype, which is often associated with oncogenic behavior, presenting a challenge to standard therapies.

Immune Reinvigoration Observed

In an impressive demonstration of paxalisib's ability to reinvigorate the immune system, early responses from patients undergoing clinical trials were particularly encouraging. The drug appeared to restore function to exhausted immune cells, enhancing the clinical landscape for treating aggressive cancer types. In TNBC, the drug demonstrated notable early activity, with the first patient in the Phase 1b trial showcasing a marked decline in CTC clusters following the initial treatment cycle.

Clinical Insights from TNBC Trials

The Phase 1b study, designed to evaluate the safety and efficacy of paxalisib in conjunction with chemotherapy and pembrolizumab, provided promising early results. Not only was there a significant decline in the number of CTC clusters, but the drug also prompted changes at the epigenetic level, steering CTCs towards less aggressive characteristics and reducing the exhaustion of CD8 T cells. Results showed a primary tumor volume reduction from 154 mm² to 36 mm², showcasing the drug's potential in not merely stabilizing but actively reducing tumor size.

A New Therapeutic Opportunity

Kazia’s findings draw attention to a previously overlooked gap in standard therapeutic approaches for HER2-positive patients—namely, the persistence of aggressive CTC clusters that continue to pose a risk for disease progression. Professor Sudha Rao from QIMR Berghofer pointed out that the existing therapies have often been ineffective in managing these clusters, leaving substantial room for improvement through the intervention of paxalisib. Moreover, the drug's dual actions—targeting mesenchymal cells and revamping immune functionality—position it as a potentially transformative addition to existing treatment paradigms, arguably broader than current applications in TNBC.

Moving Forward

With evidence indicating that both mesenchymal CTC clusters and T-cell exhaustion are shared challenges across numerous breast cancer subtypes, the implications for paxalisib extend well beyond TNBC. Emerging data suggests that even in patients benefiting from HER2-targeted therapies, aggressive CTC clusters might persist, opening a strategic path for the use of paxalisib as a supplementary treatment option.

Dr. John Friend, CEO of Kazia Therapeutics, emphasized that recent discoveries highlight the potential for paxalisib to address catalytic mechanisms of disease that remain inadequately addressed by existing treatments. As research proceeds, Kazia is poised to explore options for deploying paxalisib across various breast cancer categories, potentially alongside existing therapies like olaparib and pembrolizumab to maximize patient outcomes.

In conclusion, Kazia Therapeutics is set to redefine the landscape of breast cancer treatment with paxalisib, presenting promising avenues for improving anti-tumor responses in patients who have, until now, encountered significant hurdles in existing treatment protocols.

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