Kazia Therapeutics Ltd (ASX:KZA, NASDAQ:KZIA) is making headway in a clinical trial evaluating its lead paxalisib candidate in patients with brain metastases.
The oncology-focused drug development company is onto the expansion stage in a Phase 2 study led by the Alliance for Clinical Trials in Oncology, a US-based cancer research network sponsored by the National Cancer Institute.
Essentially, the clinical trial is focused on patients with brain metastases (cancer that has spread to the brain from elsewhere in the body) from breast cancer, lung cancer or other primary tumours.
Now, Kazia has advanced to the next stage in the breast cancer brain metastases cohort after it completed pre-specified interim analysis and met the threshold for the transition.
Looking for new therapies
“Brain metastases are a complication of several common cancers and effective treatments remain elusive,” said the study’s principal investigator and associate professor of medicine at Harvard Medical School, Priscilla Brastianos, MD.
“This study has been designed to identify potential new therapies for patients with brain metastases, using leading genomic techniques to assign patients to the most appropriate treatment,” she explained.
“We are looking forward to continuing our exploration of paxalisib in this important disease area.”
Moving to the expansion stage
Kazia plays an important role in the Phase 2 Alliance trial — a genomically-guided study of multiple therapies in patients with brain metastases.
Depending on the genetic profile of their tumour, patients are assigned one of three drug candidates: abemaciclib (from pharmaceutical company Lilly), entrectinib (from American biotech Genentech), or paxalisib (from ASX-lister Kazia).
Kazia supports the trial with a financial grant and is providing the paxalisib study drug.
For each drug-tumour combination (for example, paxalisib in patients with lung cancer brain metastases), the study envisages an initial stage of 10 patients for each subgroup (ie, breast, lung, other).
If the pre-specified response criteria are met at the interim analysis of 10 patients per subgroup, the study expands that drug-tumour combination to enrol 11 additional patients, in order to seek definitive efficacy data.
As a result, the paxalisib arm has fully recruited the breast cancer cohort for the initial prespecified interim analysis and has met the threshold for transition to the expansion stage of the study.
The initial stage of the study remains ongoing for paxalisib in lung cancer and in other tumours.
Why brain metastases?
Up to 30% of patients with metastatic cancer will develop secondary tumours (known as metastases) in the brain, and it is estimated that there are around 200,000 new cases of brain metastases each year in the United States alone.
Treatment options remain limited and the average survival of patients with brain metastases ranges from three to 27 months, depending on factors such as the location of the original tumour.
It is increasingly recognised that cancer is a complex disease, in which tumours in a similar location (eg, the breast or the lungs) may respond very differently to treatment.
Kazia says an important factor in this is the genetic profile of the tumour.
Clinical studies have started to focus on allocating patients to treatment on basis of this genetic profile, an approach that’s sometimes referred to as ‘precision medicine’ or ‘personalised medicine’.
Ultimately, the Alliance study is an example of this approach.
About Kazia
Kazia is headquartered in Sydney, Australia, and is dual-listed on the NASDAQ.
The company’s lead program is paxalisib, which is being developed to treat glioblastoma — the most common and most aggressive form of primary brain cancer in adults.
Licensed from Genentech in late 2016, paxalisib commenced recruitment to GBM AGILE, a pivotal study in glioblastoma, in January 2021. Seven additional studies are active in various forms of brain cancer.
Paxalisib was granted Orphan Drug Designation for glioblastoma from the US Food and Drug Administration in February 2018, as well as Fast Track Designation for glioblastoma in August 2020.
In addition, paxalisib was granted Rare Pediatric Disease Designation and Orphan Designation for DIPG — a rare, fast-growing brain stem tumour that usually occurs in children — in August 2020.
Kazia is also developing EVT801, a small-molecule inhibitor of VEGFR3, which was licensed from Evotec SE in April 2021.
Promisingly, preclinical data has shown EVT801 to be active against a broad range of tumour types. It has also provided compelling evidence of synergy with immuno-oncology agents.
A phase one study on the treatment candidate commenced recruitment in November 2021.