Kazia Therapeutics Limited announced the early conclusion based on positive safety and promising clinical response findings observed to date of an important two-part Phase I trial. This investigator-initiated trial evaluated the use of paxalisib (an oral PI3K/mTOR dual inhibitor) with radiation therapy for the treatment of patients with PI3K pathway mutation brain metastases from solid tumors. Part I of the study established the maximal tolerated dose (MTD) of paxalisib in combination with radiation therapy, while also demonstrating promising signs of clinical activity in all nine evaluable patients.

Part II was a follow-on expansion cohort to further evaluate safety and efficacy of the MTD (45mg daily) combined with radiation therapy in up to 12 additional patients. Detailed findings from Part II of this study are slated for submission and presentation at a forthcoming global scientific meeting, where they will contribute to the ongoing conversation about treatment options for patients with these complex brain metastases. Previous research by Dr. Jonathan Yang, Director of Metastatic Disease and Developmental Therapeutics, Department of Radiation Oncology, University of Washington School of Medicine, and others, has shown that activation of the PI3K pathway is common in brain metastases.

Moreover, PI3K pathway activation appears to result in tumor resistance to radiotherapy, which supports the rationale for evaluating paxalisib with radiotherapy in order to potentially sensitize the tumor cells to radiotherapy and achieve better disease control. Dr. Yang presented the Part I data at the 2022 Annual Conference on CNS Clinical Trials and Brain Metastases, jointly organized by the Society for Neuro-Oncology and the American Society for Clinical Oncology, held in Toronto, Canada. Last year, paxalisib was awarded Fast Track Designation (FTD) on the basis of the Part I clinical data by the United States Food and Drug Administration (FDA) for the treatment of solid tumor brain metastases harboring PI3K pathway mutations in combination with radiation therapy.

Approximately 200,000 cancer patients develop brain metastases in the United States each year. Radiotherapy is the mainstay of treatment for brain metastases, and generally consists of either stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) or some combination thereof.