Kazia Therapeutics Triples Enrollment in Phase 1b Trial of Paxalisib for Advanced Triple Negative Breast Cancer
Key Insights
Kazia Therapeutics (search) has expanded enrollment in its Phase 1b trial of paxalisib from 12 to 36 patients based on encouraging safety and tolerability data in advanced triple negative breast cancer (search).
The trial is evaluating paxalisib in combination with pembrolizumab and chemotherapy, with the expanded dataset expected to provide more meaningful assessment of objective response rate and progression-free survival.
Triple negative breast cancer (search) accounts for approximately 15-20% of all breast cancer diagnoses and is associated with poorer outcomes compared to other breast cancer subtypes.
Kazia Therapeutics (search) Limited announced plans to triple enrollment in its ongoing Phase 1b clinical trial evaluating paxalisib in combination with standard-of-care therapies for patients with advanced triple negative breast cancer (search) (TNBC (search)). The planned enrollment will increase from 12 to 36 patients following continued encouraging safety, tolerability and clinical activity data observed to date.
The expansion aims to further evaluate the safety, tolerability, dose optimization and preliminary efficacy of the paxalisib-based combination regimen with pembrolizumab and chemotherapy. The expanded dataset is expected to provide a more meaningful assessment of objective response rate (ORR), progression-free survival (PFS) and translational biomarkers, with additional clinical trial updates anticipated throughout 2026 and into 2027.
Addressing Treatment Resistance in Difficult-to-Treat Cancer
"We remain encouraged by the safety and tolerability data observed to date, and expanding enrollment allows us to generate a broader clinical and translational dataset as we advance paxalisib in difficult-to-treat advanced breast cancer, such as TNBC (search)," said Dr. John Friend, CEO of Kazia Therapeutics (search). "Paxalisib's mechanism, modulating key resistance and immune-related pathways, addresses the very reasons that current therapies fail, and we believe it holds meaningful potential for an underserved patient population."
The Phase 1b study is evaluating paxalisib in combination with established breast cancer regimens across multiple dose cohorts. The trial expansion is supported by a recently published preclinical study in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR), demonstrating that dual PI3K (search)/mTOR (search) inhibition with paxalisib altered tumor cell state and immune signaling in preclinical TNBC (search) models.
Targeting an Underserved Patient Population
TNBC (search) accounts for approximately 15 to 20 percent of all breast cancer diagnoses and is associated with poorer outcomes relative to other breast cancer subtypes. Paxalisib is an investigational brain penetrant inhibitor of the PI3K (search)/Akt (search)/mTOR (search) pathway, which is being developed to treat multiple forms of cancer.
The company's lead asset was licensed from Genentech in late 2016 and has been or is currently the subject of 10 clinical trials. A completed Phase 2/3 study in glioblastoma (search) (GBM-Agile) was reported in 2024, with discussions ongoing for designing and executing a pivotal registrational study in pursuit of standard approval.
Regulatory Recognition and Pipeline Development
Paxalisib has received multiple regulatory designations from the U.S. Food and Drug Administration, including Orphan Drug Designation for glioblastoma (search) in February 2018, Fast Track Designation for glioblastoma in August 2020, and Fast Track Designation in July 2023 for the treatment of solid tumor brain metastases (search) harboring PI3K (search) pathway mutations in combination with radiation therapy.
Other clinical trials involving paxalisib are ongoing in advanced breast cancer, brain metastases (search), diffuse midline gliomas (search), and primary central nervous system lymphoma (search), with several of these trials having reported encouraging interim data. The drug was also granted Rare Pediatric Disease Designation and Orphan Drug Designation for diffuse intrinsic pontine glioma (search) in August 2020 and for atypical teratoid/rhabdoid tumors (search) in June and July 2022, respectively.
Strategic Intellectual Property Considerations
Dr. Friend noted that while the company had planned to present scientific progress at ASCO 2026, they made the decision to withdraw their abstracts solely to protect their intellectual property position ahead of anticipated filings. "The withdrawal was not related to any safety or clinical concerns. We expect to share additional clinical and translational updates in the coming months," he stated.