Kazia Therapeutics to Present Data Highlighting Synergistic Activity Between Paxalisib and Immunotherapy in Immunotherapy-Resistant Triple Negative Breast Cancer Model at the San Antonio Breast Cancer Symposium
Kazia Therapeutics (NASDAQ: KZIA) announced data presentation at the San Antonio Breast Cancer Symposium regarding their lead candidate paxalisib for treating immunotherapy-resistant triple negative breast cancer (TNBC) and HER2 positive metastatic breast cancer with brain metastases.
The preclinical data showed promising therapeutic synergies between paxalisib and pembrolizumab (KEYTRUDA®) in immunotherapy-resistant TNBC models. Additional synergies were observed when combining paxalisib with olaparib (LYNPARZA®). In the TNBC mouse model, paxalisib combined with immunotherapy reduced tumor burden, lung metastases, and liver inflammation.
In a separate phase II trial for HER2 positive breast cancer with brain metastases, while the primary endpoint of overall response rate wasn't met, patients receiving paxalisib with trastuzumab showed a median overall survival of 16.5 months. The combination demonstrated feasible toxicity profiles consistent with PI3K/mTOR inhibitors.
Kazia Therapeutics (NASDAQ: KZIA) ha annunciato la presentazione dei dati al San Antonio Breast Cancer Symposium riguardante il loro candidato principale paxalisib per il trattamento del cancro al seno triplo negativo (TNBC) resistente all'immunoterapia e del cancro al seno metastatico HER2 positivo con metastasi cerebrali.
I dati preclinici hanno mostrato promettenti sinergie terapeutiche tra paxalisib e pembrolizumab (KEYTRUDA®) nei modelli di TNBC resistenti all'immunoterapia. Sono state osservate sinergie aggiuntive quando si combinava paxalisib con olaparib (LYNPARZA®). Nel modello murino di TNBC, paxalisib combinato con immunoterapia ha ridotto il carico tumorale, le metastasi polmonari e l'infiammazione epatica.
In uno studio di fase II separato per il cancro al seno HER2 positivo con metastasi cerebrali, mentre l'obiettivo primario del tasso di risposta globale non è stato raggiunto, i pazienti che ricevevano paxalisib con trastuzumab hanno mostrato una sopravvivenza globale mediana di 16,5 mesi. La combinazione ha dimostrato profili di tossicità sostenibili coerenti con gli inibitori PI3K/mTOR.
Kazia Therapeutics (NASDAQ: KZIA) anunció la presentación de datos en el San Antonio Breast Cancer Symposium sobre su candidato principal paxalisib para el tratamiento del cáncer de mama triplo negativo (TNBC) resistente a la inmunoterapia y del cáncer de mama metastásico HER2 positivo con metástasis cerebrales.
Los datos preclínicos mostraron sinergias terapéuticas prometedoras entre paxalisib y pembrolizumab (KEYTRUDA®) en modelos de TNBC resistentes a la inmunoterapia. Se observaron sinergias adicionales al combinar paxalisib con olaparib (LYNPARZA®). En el modelo de ratón de TNBC, paxalisib combinado con inmunoterapia redujo la carga tumoral, las metástasis pulmonares y la inflamación hepática.
En un ensayo de fase II separado para el cáncer de mama HER2 positivo con metástasis cerebrales, aunque no se alcanzó el objetivo primario de tasa de respuesta global, los pacientes que recibieron paxalisib con trastuzumab mostraron una supervivencia global mediana de 16.5 meses. La combinación demostró perfiles de toxicidad factibles consistentes con los inhibidores de PI3K/mTOR.
Kazia Therapeutics (NASDAQ: KZIA)는 San Antonio Breast Cancer Symposium에서 면역 요법 저항성 삼중 음성 유방암(TNBC) 및 뇌 전이가 있는 HER2 양성 전이성 유방암 치료를 위한 주요 후보 물질 paxalisib에 대한 데이터 발표를 했습니다.
전임상 데이터는 면역 요법 저항성 TNBC 모델에서 paxalisib와 pembrolizumab (KEYTRUDA®) 간의 유망한 치료 시너지 효과를 보여주었습니다. paxalisib와 olaparib (LYNPARZA®)를 결합했을 때 추가적인 시너지도 관찰되었습니다. TNBC 마우스 모델에서 면역 요법과 결합된 paxalisib는 종양 부담, 폐 전이 및 간 염증을 감소시켰습니다.
뇌 전이가 있는 HER2 양성 유방암을 위한 별도의 2상 시험에서, 전체 반응률이라는 주요 목표는 충족되지 않았으나, paxalisib와 trastuzumab을 받은 환자들은 16.5개월의 중앙 생존 기간을 보였습니다. 이 조합은 PI3K/mTOR 억제제와 일치하는 유효한 독성 프로필을 보여주었습니다.
Kazia Therapeutics (NASDAQ: KZIA) a annoncé la présentation de données lors du San Antonio Breast Cancer Symposium concernant leur principal candidat paxalisib pour le traitement du cancer du sein triple négatif (TNBC) résistant à l'immunothérapie et du cancer du sein métastatique HER2 positif avec métastases cérébrales.
Les données précliniques ont montré des synergies thérapeutiques prometteuses entre le paxalisib et le pembrolizumab (KEYTRUDA®) dans des modèles de TNBC résistants à l'immunothérapie. Des synergies supplémentaires ont été observées lors de la combinaison de paxalisib avec olaparib (LYNPARZA®). Dans le modèle murin de TNBC, le paxalisib combiné avec l'immunothérapie a réduit la charge tumorale, les métastases pulmonaires et l'inflammation hépatique.
Dans un essai de phase II séparé pour le cancer du sein HER2 positif avec métastases cérébrales, bien que l'objectif principal du taux de réponse global n'ait pas été atteint, les patients recevant paxalisib avec trastuzumab ont montré une survie médiane globale de 16,5 mois. La combinaison a montré des profils de toxicité viables conformes aux inhibiteurs PI3K/mTOR.
Kazia Therapeutics (NASDAQ: KZIA) gab die Präsentation von Daten beim San Antonio Breast Cancer Symposium bekannt, die ihren Hauptkandidaten paxalisib zur Behandlung von immuntherapieresistentem triple-negativem Brustkrebs (TNBC) und HER2-positivem metastasierendem Brustkrebs mit Hirnmetastasen betreffen.
Die präklinischen Daten zeigten vielversprechende therapeutische Synergien zwischen paxalisib und pembrolizumab (KEYTRUDA®) in immuntherapieresistenten TNBC-Modellen. Zusätzliche Synergien wurden beobachtet, als paxalisib mit olaparib (LYNPARZA®) kombiniert wurde. Im TNBC-Mausmodell reduzierte die Kombination von paxalisib mit Immuntherapie die Tumorlast, Lungenmetastasen und Leberentzündungen.
In einer separaten Phase-II-Studie für HER2-positiven Brustkrebs mit Hirnmetastasen wurde zwar das primäre Ziel der allgemeinen Ansprechrate nicht erreicht, jedoch wiesen Patienten, die paxalisib zusammen mit trastuzumab erhielten, eine mediane Gesamtüberlebensrate von 16,5 Monaten auf. Die Kombination zeigte verträgliche Toxizitätsprofile, die mit den PI3K/mTOR-Inhibitoren übereinstimmten.
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"Immunotherapy-resistant triple negative breast cancer represents one of the most difficult-to-treat areas of breast cancer, with a growing number of patients who have failed standard-of-care immunotherapy and require new treatment options," said John Friend, M.D., President and Chief Executive Officer of Kazia Therapeutics. "These new preclinical data highlight the potential therapeutic synergies between paxalisib and the checkpoint inhibitor, pembrolizumab (KEYTRUDA®), when used in combination in a preclinical model of immunotherapy-resistant triple negative breast cancer. Furthermore, these data also show synergies when paxalisib is combined with the PARP inhibitor, olaparib (LYNPARZA®), which is approved for the treatment of advanced BRCA-mutated HER2 negative metastatic breast cancer.
"In a second abstract, clinical investigators presented efficacy and safety data in heavily pretreated patients (median prior 8 lines of therapy) with HER2 positive breast cancer with active brain metastases. Although the primary endpoint of overall response rate (ORR) was not met, patients receiving a combination of paxalisib and trastuzumab (ENHERTU®) had a median overall survival of 16.5 months, which compares favorably versus historical control studies."
Presentation Details:
Abstract Number: | SESS-2122 | |
Title (P3-06-27): | Immunotherapy and PI3K/mTOR inhibition combination to mediate metastasis and immunotherapy resistance in triple-negative breast cancer | |
Presenting Author: | John Friend, M.D. | |
Date/Time: | December 12, 2024, 12:00-2:00 pm CT |
Conclusions: The addition of paxalisib to immunotherapy in the 4T1 TNBC mouse model reduced primary tumor burden, lung metastases, and liver inflammation whilst overcoming toxicity complications and resistance associated with standard-of-care immunochemotherapy. Paxalisib in combination with the PARP inhibitor olaparib, but not monotherapy alone, also reduced primary tumor burden and metastases. Moving forward, work is ongoing to elucidate the PI3K-mTOR mechanism of overcoming metastasis and drug resistance as well as the translation of the data into a clinical development program for patients with TNBC and advanced breast cancer.
Abstract Number: | SESS-1433 | |
Title (P5-05-04): | Final results of a phase II trial evaluating paxalisib with trastuzumab for patients (pts) with HER2 positive metastatic breast cancer with active brain metastases. | |
Presenting Authors: | Jose Leone and Co-Author(s): Jose Pablo Leone, Noah Graham, Nabihah Tayob, Heather A. Parsons, Jorge Gomez Tejeda Zañudo, Raechel Davis, Molly K. DiLullo, Jennifer A. Ligibel, Filipa Lynce, Jing Ni, Eric P. Winer, Jean Zhao, Rinath M. Jeselsohn, Nancy U. Lin | |
Date/Time: | December 13, 2024, 12:30-2:00 pm CT |
Conclusions: In this heavily pre-treated population of pts with HER2+ active BCBM, the combination of paxalisib 30 mg daily with trastuzumab was feasible, with a toxicity profile consistent with a class effect of PI3K/mTOR inhibitors. However, it was associated with minimal clinical activity.
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 programs, including paxalisib and EVT801, the potential benefits of paxalisib as an investigational PI3K/mTOR inhibitor, timing for any regulatory submissions or discussions with regulatory agencies, and the potential market opportunity for paxalisib. 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, related to regulatory approvals, and related to the impact of global economic conditions. These and other risks and uncertainties are described more fully in Kazia's Annual Report, filed on form 20-F with the United States Securities and Exchange Commission, or the SEC, and in subsequent filings with the SEC. 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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