Kazia Therapeutics Reports Early Efficacy Data from First Triple-Negative Breast Cancer Patient Receiving Paxalisib Combination Regimen achieving >50% Reduction in Circulating Tumor Cells in Phase 1b Trial
Kazia Therapeutics (NASDAQ: KZIA) has reported promising early results from its Phase 1b trial combining Paxalisib with pembrolizumab and standard chemotherapy. The first patient, a 61-year-old woman with metastatic triple-negative breast cancer, showed a greater than 50% reduction in circulating tumor cells (CTCs) after just 21 days of treatment.
The combination therapy demonstrated significant reduction in both single CTCs and CTC clusters, which are known to be 20-100X more efficient at seeding metastases than single CTCs. Notably, the treatment also reduced the mesenchymal phenotype of remaining CTCs, a characteristic associated with aggressive cancer cells.
These early results align with preclinical findings published in Molecular Cancer Therapeutics, suggesting potential effectiveness against metastatic spread. The trial continues to enroll patients to assess safety, tolerability, and pharmacodynamics.
Kazia Therapeutics (NASDAQ: KZIA) ha riportato risultati promettenti nelle prime fasi della sperimentazione di fase 1b che combina Paxalisib con pembrolizumab e la chemioterapia standard. La prima paziente, una donna di 61 anni con carcinoma mammario triplo negativo metastatico, ha mostrato una riduzione superiore al 50% delle cellule tumorali circolanti (CTC) dopo soli 21 giorni di trattamento.
La terapia combinata ha dimostrato una significativa diminuzione sia delle singole CTC che dei cluster di CTC, noti per essere da 20 a 100 volte più efficaci nel generare metastasi rispetto alle singole CTC. È importante sottolineare che il trattamento ha anche ridotto il fenotipo mesenchimale delle CTC residue, una caratteristica associata a cellule tumorali aggressive.
Questi risultati preliminari sono in linea con i dati preclinici pubblicati su Molecular Cancer Therapeutics, suggerendo un potenziale effetto contro la diffusione metastatica. La sperimentazione continua a reclutare pazienti per valutare sicurezza, tollerabilità e farmacodinamica.
Kazia Therapeutics (NASDAQ: KZIA) ha informado resultados prometedores en las primeras etapas de su ensayo de fase 1b que combina Paxalisib con pembrolizumab y quimioterapia estándar. La primera paciente, una mujer de 61 años con cáncer de mama triple negativo metastásico, mostró una reducción superior al 50% en las células tumorales circulantes (CTCs) tras solo 21 días de tratamiento.
La terapia combinada demostró una reducción significativa tanto en las CTCs individuales como en los grupos de CTCs, que son entre 20 y 100 veces más eficientes en la formación de metástasis que las CTCs individuales. Cabe destacar que el tratamiento también redujo el fenotipo mesenquimal de las CTCs restantes, una característica asociada con células cancerosas agresivas.
Estos resultados iniciales coinciden con los hallazgos preclínicos publicados en Molecular Cancer Therapeutics, sugiriendo un posible efecto contra la diseminación metastásica. El ensayo continúa reclutando pacientes para evaluar la seguridad, tolerabilidad y farmacodinámica.
Kazia Therapeutics (NASDAQ: KZIA)는 Paxalisib와 pembrolizumab, 표준 화학요법을 병용한 1b상 임상시험에서 유망한 초기 결과를 보고했습니다. 첫 번째 환자인 61세의 전이성 삼중음성 유방암 여성 환자는 단 21일 치료 후 순환 종양 세포(CTC)가 50% 이상 감소하는 모습을 보였습니다.
이 병용 요법은 단일 CTC와 CTC 클러스터 모두에서 상당한 감소를 나타냈으며, CTC 클러스터는 단일 CTC보다 전이 형성 효율이 20~100배 높은 것으로 알려져 있습니다. 특히, 남아있는 CTC의 중간엽 표지형도 감소시켰는데, 이는 공격적인 암세포와 관련된 특징입니다.
이 초기 결과는 Molecular Cancer Therapeutics에 발표된 전임상 연구 결과와 일치하며, 전이 확산에 대한 잠재적 효과를 시사합니다. 임상시험은 계속해서 안전성, 내약성 및 약력학적 특성을 평가하기 위해 환자를 모집 중입니다.
Kazia Therapeutics (NASDAQ : KZIA) a annoncé des résultats prometteurs lors de la phase 1b de son essai combinant Paxalisib avec le pembrolizumab et la chimiothérapie standard. La première patiente, une femme de 61 ans atteinte d’un cancer du sein triple négatif métastatique, a présenté une réduction de plus de 50 % des cellules tumorales circulantes (CTC) après seulement 21 jours de traitement.
Cette thérapie combinée a montré une réduction significative des CTC individuelles ainsi que des amas de CTC, connus pour être 20 à 100 fois plus efficaces pour initier des métastases que les CTC isolées. Notamment, le traitement a également réduit le phénotype mésenchymateux des CTC restantes, une caractéristique associée aux cellules cancéreuses agressives.
Ces résultats préliminaires sont cohérents avec les données précliniques publiées dans Molecular Cancer Therapeutics, suggérant une efficacité potentielle contre la dissémination métastatique. L’essai continue de recruter des patients afin d’évaluer la sécurité, la tolérance et la pharmacodynamie.
Kazia Therapeutics (NASDAQ: KZIA) hat vielversprechende erste Ergebnisse aus seiner Phase-1b-Studie berichtet, in der Paxalisib mit Pembrolizumab und Standard-Chemotherapie kombiniert wird. Die erste Patientin, eine 61-jährige Frau mit metastasiertem triple-negativem Brustkrebs, zeigte nach nur 21 Tagen Behandlung eine Reduktion der zirkulierenden Tumorzellen (CTCs) um mehr als 50%.
Die Kombinationstherapie führte zu einer signifikanten Verringerung sowohl einzelner CTCs als auch von CTC-Clustern, die bekanntlich 20- bis 100-mal effizienter Metastasen bilden als einzelne CTCs. Bemerkenswert ist, dass die Behandlung auch das mesenchymale Phänotyp der verbleibenden CTCs reduzierte, ein Merkmal aggressiver Krebszellen.
Diese frühen Ergebnisse stimmen mit präklinischen Daten überein, die in Molecular Cancer Therapeutics veröffentlicht wurden, und deuten auf eine potenzielle Wirksamkeit gegen die metastatische Ausbreitung hin. Die Studie läuft weiter und rekrutiert Patienten, um Sicherheit, Verträglichkeit und Pharmakodynamik zu bewerten.
- First patient showed >50% reduction in circulating tumor cells after only 21 days
- Treatment reduced both single CTCs and CTC clusters, which are crucial for metastasis
- Results validate preclinical findings and demonstrate mechanistic synergy
- Early efficacy seen in triple-negative breast cancer, an aggressive cancer type
- Data is very early stage from only one patient
- Long-term efficacy and safety data still pending
- Broader patient response patterns yet to be established
Insights
Early Phase 1b data shows Paxalisib combination reduced circulating tumor cells by >50% in triple-negative breast cancer, suggesting promising anti-metastatic potential.
The preliminary data from Kazia's Phase 1b trial represents an intriguing early signal in triple-negative breast cancer (TNBC), one of the most aggressive breast cancer subtypes with limited treatment options. A >50% reduction in circulating tumor cells (CTCs) after just 21 days is noteworthy, particularly since CTCs are established biomarkers of metastatic potential.
What makes this finding particularly significant is the reduction in CTC clusters, which are 20-100 times more efficient at seeding metastases than individual CTCs. Standard chemotherapy often causes a transient increase in CTCs during the first cycle before normalizing, while immunotherapy typically shows delayed effects on these metrics. The rapid reduction in both metrics suggests potential mechanistic synergy between Paxalisib (a PI3K/mTOR pathway inhibitor) and pembrolizumab (immune checkpoint inhibitor).
However, several important caveats must be considered. This represents data from only a single patient, and TNBC is known for heterogeneous responses. CTC reduction, while promising as a surrogate marker, doesn't necessarily translate to improved progression-free or overall survival. The true test will be radiographic responses and longer-term outcomes as the trial progresses.
The observed reduction in mesenchymal phenotype is biologically interesting, as this trait is associated with treatment resistance and metastatic capability. If consistent across more patients, this could indicate the combination is addressing one of the fundamental challenges in treating aggressive TNBC.
The early data in this first patient closely mirror the mechanistic preclinical findings published in Molecular Cancer Therapeutics (https://aacrjournals.org/mct/article/doi/10.1158/1535-7163.MCT-24-0693/762979/Depleting-the-Action-of-EZH2-through-PI3K-mTOR), which highlight that Paxalisib, when combined with immunotherapy, significantly disrupted both single CTCs and multicellular clusters in preclinical models.
Key Highlights
- Patient Profile: 61-year-old female, metastatic triple-negative breast cancer (lung metastasis).
- Investigational Regimen: Paxalisib, pembrolizumab, and chemotherapy.
- Results at Day 21 (End-of-Cycle 1):
- >
50% reduction in total CTC count. - Comparable reduction in CTC clusters—these aggregates are associated with heightened metastatic potential.
- 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 potential for potent CTC mobilization suppression by this combination.
Clinical Significance of Patient Data
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 with exceptional efficiency. Notably, standard chemotherapy has been shown in some studies 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.
In this case, the combination regimen of Paxalisib and immunotherapy achieved a rapid reduction in both CTC numbers and clusters as well as a reduction in the mesenchymal phenotype—an outcome not typically seen with chemotherapy or immunotherapy alone after only 21 days of treatment. This early clinical data reflects mechanistic synergy consistent with the preclinical data described in the MCT manuscript.
Dr. John Friend, MD, Chief Executive Officer of Kazia Therapeutics, said "It is very exciting to see our extensive preclinical research translate into such positive early data in this first patient receiving a combination of Paxalisib and immunotherapy. The degree of reduction in tumor cell dissemination markers in just 21 days gives us strong reason for optimism as we continue this clinical trial."
Dr. Friend continued "CTC clusters are emerging as key drivers of metastatic spread—they're 20–100X more efficient at seeding than single CTCs—and the sharp decline we're seeing is truly encouraging. We believe this combination may offer a meaningful early intervention against systemic disease progression."
Next Steps
- Explore potential relationship between CTC kinetics and radiographic responses
- Enrollment continues in the Phase Ib study, expanding cohort size to assess safety, tolerability, and pharmacodynamics
- Planned comprehensive analysis of 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
For investor and media, please contact Alex Star, Managing Director LifeSci Advisors LLC, Astarr@lifesciadvisors.com, +1-201-786-8795.
About Kazia Therapeutics Limited
Kazia Therapeutics Limited (NASDAQ: KZIA) is an oncology-focused drug development company, based in
Forward-Looking Statements
This announcement may contain forward-looking statements, which can generally be identified as such by the use of words such as "may," "will," "estimate," "future," "forward," "anticipate," or other similar words. Any statement describing Kazia's future plans, strategies, intentions, expectations, objectives, goals or prospects, and other statements that are not historical facts, are also forward looking statements, including, but not limited to, statements regarding: the timing for results and data related to Kazia's clinical and preclinical trials, Kazia's strategy and plans with respect to its paxalisib program, the potential results of its Phase 1b clinical trial evaluating paxalisib in combination with olaparib or pembrolizumab for patients with advanced breast cancer, the potential benefits of paxalisib as an investigational PI3K/mTOR inhibitor, timing for any regulatory submissions or discussions with regulatory agencies, the potential market opportunity for paxalisib and Kazia's intent and efforts to regain and/or maintain compliance with the applicable Nasdaq continued listing requirements and standards. Such statements are based on Kazia's current expectations and projections about future events and future trends affecting its business and are subject to certain risks and uncertainties that could cause actual results to differ materially from those anticipated in the forward-looking statements, including risks and uncertainties associated with clinical and preclinical trials and product development, including the risk that interim or early data may not be consistent with final data, risks related to regulatory approvals, risks related to the impact of global economic conditions, and risks related to Kazia's ability to regain and/or maintain compliance with the applicable Nasdaq continued listing requirements and standards. These and other risks and uncertainties are described more fully in Kazia's Annual Report, filed on form 20-F with the SEC, and in subsequent filings with the United States Securities and Exchange Commission. Kazia undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required under applicable law. You should not place undue reliance on these forward-looking statements, which apply only as of the date of this announcement.
This announcement was authorized for release by Dr John Friend, CEO
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