Kazia Therapeutics Reports Early Conclusion of Clinical Trial After Reaching Primary Endpoint

PUBLISHED

FEB 21, 2024 7:30AM EST

Paxalisib plus Radiotherapy Data Shows Promise for Treating Patients with PI3K Pathway Mutation Brain Metastases

SYDNEY, Feb. 21, 2024 /PRNewswire/ -- Kazia Therapeutics Limited (NASDAQ: KZIA), a biotechnology company specializing in oncology, today 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.

After reviewing the Part II patient data generated to date, the three lead investigators have determined that the primary endpoint of the study has been reached. In addition, the investigators continued to observe encouraging signs of clinical response in patients in the expansion cohort. 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.

Kazia's CEO, Dr. John Friend, shared his enthusiasm: "We are extremely excited about these findings, which include not only encouraging safety data but also some promising efficacy signals for paxalisib in combination with radiation therapy. We are now preparing to engage with the Food and Drug Administration to discuss the data and seek guidance on the conduct of a pivotal registration study, with the goal of rapidly progressing paxalisib's development to potentially provide a more effective treatment option for patients with 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. The efficacy in patients who receive WBRT differs according to the type of tumor and the number and volume of brain metastases, but several recent publications cite overall response rates of 20-45%. The increasing incidence of brain metastasis and the low response rates to existing treatments underscores the need for new treatment options.