Sydney, July 10, 2024 -- Kazia Therapeutics Limited (NASDAQ: KZIA), an oncology-focuseddrug development company, is pleased to announce results from GBM-AGILE, a phase II/IIIstudy that included an evaluation of paxalisib versus standard of care (SOC) for patients withglioblastoma (NCT03522298), a life-threatening brain cancer, where there is an urgentunmet need for new therapeutics.
GBM AGILE STUDY
GBM AGILE is an adaptive phase II/III global trial sponsored by the Global Coalition forAdaptive Research (GCAR), a nonprofit organization comprised of some of the world’sforemost clinical, translational, and basic science researchers, from institutions such asMemorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute. The trial isdesigned to efficiently screen for and characterize the response of glioblastoma (GBM)patients to novel investigative agents. Utilizing a complex innovative design, Bayesianprinciples are applied to the primary endpoint (Overall Survival) comparison of theinvestigational agents to patients receiving Standard of Care (SOC) enrolled from the studystart (also referred to as cumulative control population). In general, secondary analyses andendpoints are assessed based on established statistical models in comparison to the controlpatients enrolled at the same time as the investigational agent (concurrent controlpopulation).
Paxalisib is the third drug candidate to complete its evaluation in the study and wasevaluated in newly diagnosed glioblastoma patients with unmethylated MGMT promoterstatus as well as in patients with recurrent disease.
GBM AGILE Paxalisib Results
Kazia CEO, Dr John Friend stated, “We are excited to have shown a 3.8 month improvementin overall survival, an approximate 33% improvement, for newly diagnosed unmethylatedpatients with GBM compared to the concurrent standard of care arm. Having comparableOverall Survival data across two independent studies is a compelling outcome in this difficultto treat glioblastoma population. We look forward to discussing possible approaches for anaccelerated approval pathway for paxalisib with the FDA.”
A total of 313 newly diagnosed unmethylated (NDU) patients and recurrent patients beingtreated at top US cancer hospitals were randomized in Stage 1 to either a paxalisibtreatment arm (60 mg/day) or the SOC concurrent control arm from January 2021 to May2022. The cumulative control arm was enrolled from July 2019 (GBM Agile study start date)to May 2022.
For the primary analysis the median Overall Survival (OS) was 14.77 months for paxalisibtreated NDU patients (n=54) versus 13.84 months for cumulative SOC NDU patients (n=75).
For a prespecified secondary analysis in the NDU patients, median OS was 15.54 months inthe paxalisib arm (n=54) versus 11.89 months for concurrent SOC (n=46). In addition, aprespecified sensitivity analysis in NDU patients showed similar median OS differencebetween paxalisib treated patients (15.54 months) and concurrent SOC patients (11.70months).
The secondary analysis results are consistent with the previously reported Companysponsored phase II study, where median OS was 15.7 months (n=27) for paxalisib treatedNDU patients compared to 12.7 months historically reported with temozolomide in thispatient group (Wen 2022).
Paxalisib was well tolerated in GBM-AGILE, and no new safety signals were identified in thispatient population.
An efficacy signal was not detected in the recurrent disease population (median OS of 9.69months for concurrent SOC (n=113) versus 8.05 months for paxalisib (n=100). Similar resultsin this population have been reported in the other two drug candidates that havecompleted the GBM AGILE trial. Kazia is currently pursuing further analyses of this data toelucidate potential signals for further consideration.
Based on the totality of data available from all completed paxalisib clinical studies in newlydiagnosed unmethylated GBM patients, Kazia will request a meeting with the US Food &Drug Administration (FDA) to discuss the results and determine if a potential path toaccelerated approval is appropriate for paxalisib.
Paxalisib has previously received orphan drug designation and fast track designation fromthe FDA for glioblastoma in unmethylated MGMT promoter status patients, followingradiation plus temozolomide therapy.
Full data including secondary endpoints from the paxalisib arm of the GBM AGILE study isexpected to be presented at a scientific meeting later this year.
About Kazia Therapeutics Limited
Kazia Therapeutics Limited (NASDAQ: KZIA) is an oncology-focused drug development company,based in Sydney, Australia.
Our lead program is paxalisib, an investigational brain-penetrant inhibitor of the PI3K / Akt / mTORpathway, which is being developed to treat multiple forms of brain cancer. Licensed from Genentechin late 2016, paxalisib is or has been the subject of ten clinical trials in this disease. A completedPhase 2 study in glioblastoma reported early signals of clinical activity in 2021, and a pivotal study inglioblastoma, GBM AGILE, has been completed with presentation of paxalisib arm data expectedlater in 2024 at a major medical conference. Other clinical trials involving paxalisib are ongoing inbrain metastases, diffuse midline gliomas, and primary CNS lymphoma, with several of these trialshaving reported encouraging interim data.
Paxalisib was granted Orphan Drug Designation for glioblastoma by the FDA in February 2018, andFast Track Designation (FTD) for glioblastoma by the FDA in August 2020. Paxalisib was also grantedFTD in July 2023 for the treatment of solid tumour brain metastases harboring PI3K pathwaymutations in combination with radiation therapy. In addition, paxalisib was granted Rare PediatricDisease Designation and Orphan Drug Designation by the FDA for diffuse intrinsic pontine glioma inAugust 2020, and for atypical teratoid / rhabdoid tumours in June 2022 and July 2022, respectively.
Kazia is also developing EVT801, a small-molecule inhibitor of VEGFR3, which was licensed fromEvotec SE in April 2021. Preclinical data has shown EVT801 to be active against a broad range oftumour types and has provided evidence of synergy with immuno-oncology agents. A Phase I studyis ongoing and presentation of preliminary data at a medical conference is anticipated in CY2024.For more information, please visit www.kaziatherapeutics.com or follow us on X @KaziaTx.