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Kazia Therapeutics has announced the regulatory approval and launch of its new clinical trial evaluating the combination of paxalisib and immunotherapy in patients with advanced breast cancer. According to Kazia, the trial is the first known study conducted to assess the safety and efficacy of paxalisib in combination with Keytruda (pembrolizumab) or Lynparza (olaparib) in women with triple negative breast cancer.1
The newly announced trial, ABC-Pax, is a Phase Ib multi-cener, open-label study that will enroll 24 patients from top cancer centers in Queensland, Australia. Patients will receive the combination therapy for up to 12 months.
In a press release, QIMR Berghofer’s Professor Sudha Rao said, “There is no cure for triple negative breast cancer and the life expectancy for these women is tragically short. We want to identify treatments to extend the duration and quality of life of these patients. The hope is to prolong patient survival through the new combined therapy, which targets the dormant cancer cells that drive the spread and recurrence of the disease and rejuvenates the immune system to more effectively fight the cancer.”
John Friend, MD, CEO of Kazia Therapeutics added, “The novelty of the science that Professor Rao has proposed with this dual combination of paxalisib and immunotherapy could advance the treatment of women with aggressive breast cancer, and we are excited to support this unique clinical study.”
Pre-clinical research led by QIMR Berghofer scientists in collaboration with Kazia Therapeutics showed the paxalisib-immunotherapy combination approach triggers a novel molecular program by epigenetic re-programming of dormant cancer cells, making them visible to the immune system, while also reinvigorating the immune cells to fight the tumor cells.
Earlier in October 2024, Kazia shared Phase I data of paxalisib and radiation therapy (RT) being evaluated in patients for the treatment of solid tumor brain metastases or leptomeningeal metastases harboring PI3K pathway mutations.2
Results showed that treatment with paxalisib and RT achieved a 67% partial response, with over two-thirds of the patients at maximum tolerated dose (MTD) achieving intracranial response.
The Phase I study was a two-part, investigator-initiated trial. In part one, the study established the MTD of paxalisib in combination with radiation therapy, while also demonstrating promising signs of clinical activity in all nine evaluable patients. Following, part two was a follow-on expansion cohort to further evaluate safety and efficacy of the MTD combined with radiation therapy in up to 12 additional patients.
In an earlier press release from the time, Friend said, “The encouraging response rates observed from this Phase I study suggests that the concurrent administration of the investigational brain penetrant PI3K inhibitor, paxalisib, in combination radiation therapy appears to be a viable treatment approach for addressing the tumor radioresistance in patients harboring PI3K pathway mutations. Additional data, including circulating tumor DNA from this study will be presented at an upcoming 2024 scientific congress and discussions for a potential pivotal registration study to evaluate this unique combination therapy for patients with PI3K mutant brain metastases are ongoing.”
References
1. Kazia Therapeutics announces the launch of a groundbreaking trial with paxalisib in combination with immunotherapy in women with advanced breast cancer. News release. Kazia Therapeutics. January 30, 2025. Accessed January 31, 2025. https://www.prnewswire.com/news-releases/kazia-therapeutics-announces-the-launch-of-a-groundbreaking-trial-with-paxalisib-in-combination-with-immunotherapy-in-women-with-advanced-breast-cancer-302364230.html
2. Kazia Therapeutics Announces Presentation of Promising Phase I Data Evaluating Concurrent Paxalisib and Radiation Therapy in Patients with Solid Tumor Brain Metastases or Leptomeningeal Metastases Harboring PI3K Pathway Mutations at the American Society for Radiation Oncology 66th Annual Meeting. News release. Kazia Therapeutics. October 2, 2024. Accessed January 31, 2025. https://www.prnewswire.com/news-releases/kazia-therapeutics-announces-presentation-of-promising-phase-i-data-evaluating-concurrent-paxalisib-and-radiation-therapy-in-patients-with-solid-tumor-brain-metastases-or-leptomeningeal-metastases-harboring-pi3k-pathway-mutations–302265538.html