On December 11, 2024 Kazia Therapeutics Limited (NASDAQ: KZIA), an oncology-focused drug development, reported that data from two abstracts will be presented at the San Antonio Breast Cancer Symposium highlighting the activity the Company’s lead product candidate, paxalisib, for the potential treatment of immunotherapy-resistant triple negative breast cancer (TNBC) and HER2 positive metastatic breast cancer with active brain metastases (Press release, Kazia Therapeutics, DEC 11, 2024, View Source [SID1234649047]).

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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.