On October 2, 2024 Kazia Therapeutics Limited (NASDAQ: KZIA), an oncology-focused drug development company, reported the presentation of data from a Phase I study (NCT04192981) evaluating concurrent paxalisib and radiation therapy (RT) in patients for the treatment of solid tumor brain metastases (BM) or leptomeningeal metastases (LM) harboring PI3K pathway mutations at the American Society for Radiation Oncology 66th Annual Meeting (ASTRO 2024), which is taking place from September 29 – October 2, 2024, in Washington, D.C (Press release, Kazia Therapeutics, OCT 2, 2024, View Source [SID1234646999]).

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"The encouraging response rates observed from this Phase 1 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," said John Friend, M.D., Chief Executive Officer of Kazia Therapeutics. "Additional data, including circulating tumor DNA (ctDNA) 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."

Presentation details:

Title:    Multi-Center Phase I Study of Concurrent Paxalisib and Radiation Therapy in Patients with Solid Tumor Brain Metastases (BM) or Leptomeningeal Metastases (LM) Harboring PI3K Pathway Mutations
Presenter: Brandon S. Imber, M.D., M.A., Memorial Sloan Kettering Cancer Center
Abstract 1094
Scientific Session Title: CNS 4: Brain Mets and LMD
Session Date/Time: October 1, 5:15-6:15 PM ET
Summary Results from Part II of Phase 1 Study

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Concurrent daily administration of paxalisib with brain radiotherapy was generally well-tolerated at a maximum dose of 45 mg per day in advanced solid tumor patients with brain metastases and PI3K pathway mutations;

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The most commonly reported adverse events in the study were nausea, vomiting and hyperglycemia;

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Established proof-of-principle for molecularly-selected, rational combination studies in radiation oncology to assess safety and ultimately efficacy;

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Treatment with 45mg paxalisib and radiotherapy demonstrated a 67% PR; and

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Over two-thirds of the patients at MTD achieved intracranial response which compares favorably to historical response rates for WBRT alone.

The Phase 1 study (n=17 evaluable) was a two-part, investigator-initiated trial evaluating the use of paxalisib with radiation therapy for the treatment of patients with PI3K pathway mutation brain metastases from solid tumors. Part I of 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. 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.

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.