Kazia Therapeutics KZIA on Wednesday reported preliminary results from the first patient in its Phase 1b trial evaluating a combination regimen of Paxalisib, Merck & Co Inc’s MRK Keytruda (pembrolizumab), and standard chemotherapy after completing Cycle 1 (21 days) of dosing.
The patient, a 61-year-old woman with metastatic triple-negative breast cancer localized to the left upper lobe of the lung, has shown highly encouraging preliminary results at 21 days, with a >50% reduction in circulating tumor cells (CTCs) and a notable decrease in CTC clusters.
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The early data in this first patient closely mirror the mechanistic preclinical findings published in Molecular Cancer Therapeutics, which highlight that Paxalisib, when combined with immunotherapy, significantly disrupted both single CTCs and multicellular clusters in preclinical models.
Key Highlights
There has been a reduction of more than 50% in the total CTC count.
A similar decrease in circulating tumor cell (CTC) clusters is observed, and these aggregates are linked to an increased potential for metastasis.
Reduction in the mesenchymal phenotype of the remaining CTCs; this phenotype is one of the hallmarks of aggressive metastatic seeding cancer cells.
First-in-human data support the potential for potent CTC mobilization suppression by this combination.
Why It Matters
CTC clusters have long been recognized as critical mediators of metastasis and markers of poor prognosis. They are known to resist apoptosis, evade immune detection, and seed new tumor sites.
Some studies have shown standard chemotherapy to transiently increase CTC and cluster counts within the first cycle, with levels sometimes doubling before normalizing after cycle two.
In contrast, immunotherapy alone has demonstrated variable impact, often showing delayed or modest effects on CTCs, likely due to immune-mediated mechanisms over weeks to months.
What Are The Next Steps?
Explore the potential relationship between CTC kinetics and radiographic responses.
Enrollment continues in the Phase 1b study, expanding cohort size to assess safety, tolerability, and pharmacodynamics.
Planned a comprehensive analysis of the immune microenvironment and CTC kinetics across all patients through serial monitoring.
Longer-term follow-up will include imaging, progression-free survival, and assessment of correlation with molecular biomarkers.
Price Action: KZIA stock is up 22.9% at $8.39 at the last check on Wednesday.
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