Early Phase 1b data show five objective responses among six evaluable patients with advanced triple-negative breast cancer treated with paxalisib.

Five patients achieved objective responses

Kazia Therapeutics has reported a 100% clinical benefit rate among the first six evaluable patients treated with paxalisib for Stage IV triple-negative breast cancer (TNBC).

Five patients achieved an objective response, comprising one complete response and four partial responses, giving an objective response rate of 83%. The sixth patient had stable disease.

The results come from an ongoing Phase 1b study evaluating paxalisib in combination with pembrolizumab and chemotherapy in patients with advanced metastatic TNBC.

The company said there were no treatment-related serious adverse events among the six patients and no grade 3 or higher hyperglycaemia, stomatitis or mucositis reported.

The findings are early and based on a small number of patients, so further study will be needed to determine whether the response rate is maintained in a larger population.

Complete metabolic response reported

One 44-year-old woman with Stage IV TNBC achieved a complete metabolic response and has had no evidence of disease since November 2025, according to Kazia.

The response remained ongoing at the most recent assessment and was accompanied by changes in circulating tumour cell clusters and exhausted CD8+ T cells.

Clinical responses were reported across metastatic disease sites including the lung, liver, bone, lymph nodes and central nervous system.

Kazia said responses emerged from approximately three months after randomisation, although the small patient population means these observations cannot yet establish how paxalisib performs across the wider TNBC population.

Paxalisib is an investigational oral inhibitor of the PI3K/Akt/mTOR pathway. The drug is designed to inhibit signalling involved in cancer cell growth and survival, while the current study is also investigating its potential effects on tumour-associated immune responses.

Changes seen in tumour and immune markers

Translational analyses showed reductions in terminally exhausted CD8+ T cells in all six patients, with a median reduction of 51% approximately three weeks after treatment.

These cells are a dysfunctional population of cytotoxic T cells that can have reduced ability to recognise and kill cancer cells. Total CD8+ T cell counts remained unchanged, which the company said suggests the observed reduction in exhausted cells may reflect changes in their state rather than their removal.

Blood-based analyses measuring proteins, RNA and other markers also showed changes associated with anti-tumour immune activity and reduced immune exhaustion, alongside evidence of PI3K-AKT pathway target engagement.

All six patients also demonstrated reductions in circulating tumour cell clusters, with a median reduction of 83% within six to seven weeks of treatment.

Circulating tumour cell clusters are groups of cancer cells found in the bloodstream that can contribute to the development of metastatic disease.

John Friend, CEO of Kazia Therapeutics, said: “Across the six evaluable patients treated, every one of them has benefited, and we haven’t seen a single serious adverse event tied to paxalisib.”

He added: “We’ve also demonstrated meaningful improvements in terminally exhausted T cells and drastic reductions in circulating tumor cell (CTC) clusters, providing early evidence that paxalisib may be addressing biological mechanisms associated with treatment resistance and metastasis.”

The Phase 1b study is continuing to evaluate paxalisib in combination with pembrolizumab and chemotherapy in advanced metastatic TNBC.

Kazia expects enrolment to be completed by July 2027, with further interim clinical updates expected during 2026 and 2027.