Kintara Therapeutics Inc (NASDAQ:KTRA) and Kazia Therapeutics Limited (ASX:KZA) (NASDAQ:KZIA) announced Wednesday that their drugs, VAL-083 and paxalisib, respectively, have been activated for an adaptive platform recurrent glioblastoma (GBM) trial.
The companies, in collaboration with the Global Coalition for Adaptive Research (GCAR), are entering the GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment) trial that opened in July and has screened more than 370 patients to date.
GBM is the most deadly form of brain cancer, and this trial is designed to test multiple therapies in newly diagnosed patients.
Kintara’s VAL-083 will be enrolling in newly-diagnosed unmethylated (NDUM) and recurrent GBM arms of the trial, the company said. It will also be the first compound to be evaluated for patients with newly diagnosed methylated MGMT. Kazia’s paxalisib will be enrolling in NDUM and recurrent GBM as well.
“The opportunity to participate in the GBM AGILE trial is an important milestone for Kintara, as it provides VAL-083, our lead compound, with multiple shots on goal in this cost-effective, adaptive designed registration study with full FDA/regulatory support,” Kintara CEO Saiid Zarrabian said in a statement. “VAL-083 is the only therapeutic agent participating in the study being evaluated in all 3 patient subtypes which ... may accelerate VAL-083’s time to pivotal trial completion and potential regulatory submission by up to 18 months.”
The trial is expected to target 150-200 patients for rapid enrollment, Zarrabian added.
GBM AGILE is an international trial designed to more rapidly identify and confirm effective therapies for patients with glioblastoma through response-adaptive randomization and a seamless phase 2/3 design. The trial is conducted under a master protocol, allowing multiple therapies or combinations of therapies from different pharmaceutical partners to be evaluated simultaneously, the company said.
“GBM AGILE is an innovative clinical trial approach that enables us to simultaneously and dynamically study the effects of multiple new drug candidates,” said James Perry, a professor of neurology at the University of Toronto Sunnybrook Research Institute involved in the Kintara arm. “With the inclusion of paxalisib and VAL-083 for NDUM and recurrent GBM patients, as well as VAL-083 for the additional methylated GBM patient group, we are excited to offer all GBM patients access to these latest therapies.”
The new interventions are opening first at Henry Ford Cancer Institute in Detroit and will subsequently open at over 30 trial sites in the US, the company said, with sites in Canada, Europe and China expected to follow.
VAL-083 and paxalisib
Kintara’s VAL-083 is a small molecule bifunctional alkylating agent that crosses the blood-brain barrier. The drug has been granted Orphan Drug Designation for GBM by the Food and Drug Administration (FDA) and European Medicines Agency (EMA), in addition to FDA Fast Track Designation in recurrent GBM.
Additionally, VAL-083 has also been granted Orphan Drug Designations for medulloblastoma and ovarian cancer by the FDA and is approved as a cancer chemotherapeutic in China for the treatment of chronic myelogenous leukemia and lung cancer.
“Kintara is pleased to participate in the groundbreaking GBM AGILE trial, and is excited to be the first investigational drug selected for newly diagnosed methylated GBM in the study,” Zarrabian said. “With VAL-083 being evaluated in all subtypes we expect that this study will generate important insights into VAL-083’s potential to improve health outcomes for all GBM patients.”
Kazia’s paxalisib is a small molecule inhibitor of the PI3K/AKT/mTOR pathway and has been shown to have an anti-tumor effect in animal models of glioblastoma. The PI3K pathway appears to be disordered in more than 85% of cases of glioblastoma, making this pathway a high-potential target for new glioblastoma therapies, the company said.
Paxalisib was granted Orphan Drug Designation for glioblastoma by the FDA in 2018 and Fast Track Designation for glioblastoma 2020. The drug was also granted Rare Pediatric Disease Designation and Orphan Designation for diffuse intrinsic pontine glioma.
“This is an important and innovative effort, utilizing a platform approach and cutting-edge adaptive design to rapidly identify whether drugs such as paxalisib can bring benefit to patients with glioblastoma,” Kazia CEO James Garner said. “There is a profound need for new therapeutic options in this disease, and GBM AGILE has been designed to accelerate the process of making new drugs available to patients and clinicians.”
Contact Andrew Kessel at email@example.com
Follow him on Twitter @andrew_kessel