Kazia Therapeutics Doses First Patient in PNOC035 Phase 2 Trial of Paxalisib Plus Gemcitabine for Recurrent Pediatric AT/RT
核心洞察
Kazia Therapeutics (搜索) announced the first patient has been dosed in Arm A of PNOC035, a Phase 2 platform study evaluating paxalisib plus gemcitabine in recurrent or progressive AT/RT.
The study enrolls patients ages 1 to 39 with atypical teratoid/rhabdoid tumor (搜索), an aggressive pediatric brain cancer for which no approved therapies currently exist.
Preclinical data showed the combination increased median survival nearly four-fold (22 to 82.5 days; p<0.0001) in an orthotopic AT/RT model.
Kazia Therapeutics (搜索) Limited (NASDAQ: KZIA) announced that the first patient has been dosed in Arm A of PNOC035, a Phase 2 platform study evaluating paxalisib in combination with gemcitabine for patients ages 1 to 39 with recurrent or progressive atypical teratoid/rhabdoid tumor (搜索) (AT/RT). AT/RT is widely recognized as one of the most aggressive forms of pediatric brain cancer, and no approved therapies currently exist for the recurrent or progressive setting.
PNOC035 is conducted by the Pediatric Neuro-Oncology Consortium (搜索) (PNOC) as an open-label, multi-center platform study. In Arm A, patients receive oral, once-daily paxalisib in combination with intravenous gemcitabine on Days 1, 8 and 15 of each 28-day treatment cycle. The platform design allows multiple treatment arms to be evaluated within a shared trial infrastructure, with patients enrolling in an arm based on availability and arm-specific eligibility criteria.
Preclinical Rationale
The advancement of paxalisib plus gemcitabine into the multicenter PNOC035 study is supported by preclinical findings previously presented at ISPNO, AACR and Neuro-Oncology meetings. The combination increased median survival nearly four-fold, from 22 to 82.5 days (p<0.0001), in an orthotopic AT/RT preclinical model and demonstrated complementary anti-tumor activity across multiple AT/RT cell lines. These findings extend paxalisib's pediatric neuro-oncology development beyond diffuse midline glioma into another area of significant unmet need.
Regulatory Status
Paxalisib has been granted both Orphan Drug Designation and Rare Pediatric Disease Designation by the U.S. Food and Drug Administration (FDA) for AT/RT. These designations do not constitute FDA approval or endorsement of any therapeutic claim. If paxalisib were to receive marketing approval for this indication, which would require successful completion of clinical development and FDA regulatory approval, Kazia could become eligible to receive a pediatric priority review voucher from the FDA.
"AT/RT typically affects infants and very young children, and families facing this devastating diagnosis have limited treatment options," said Dr. John Friend II, Chief Executive Officer of Kazia Therapeutics (搜索). "Despite decades of research, there are still no approved therapies for recurrent or progressive AT/RT, underscoring the urgent need for new treatment options. We've remained committed to pediatric brain cancer because this is an area where the need is especially great and the options are often fewest. Reaching this milestone with the PNOC035 team is a meaningful step forward, and we look forward to working closely with PNOC as enrollment progresses."
Paxalisib Development Program
Paxalisib is an investigational brain penetrant inhibitor of the PI3K/Akt/mTOR (搜索) pathway, licensed from Genentech in late 2016, and has been the subject of over 15 clinical trials. A completed Phase 2/3 study in glioblastoma (GBM AGILE) was reported in 2024, with discussions ongoing for designing and executing a pivotal registrational study in pursuit of a standard approval. Other clinical trials involving paxalisib are ongoing in advanced breast cancer, brain metastases, diffuse midline gliomas, and primary central nervous system lymphoma, with several of these trials having reported encouraging interim data.
Additional information about PNOC035 is available on ClinicalTrials.gov (NCT07447076).