Biotechnology company Kazia Therapeutics (ASX: KZA) has taken a definitive step towards proving the safety and efficacy of its investigational new drug GDC-0084, after announcing a “state of the art” phase 1 clinical trial to be conducted at the Memorial Sloan Kettering Cancer Center (MSK) in the US.
Importantly for Kazia, the trial is to be led by MSK and takes the total tally of ongoing clinical trials being conducted with GDC-0084 up to five – each in different forms of brain cancer.
As its lead developmental drug, GDC-0084 is being developed to treat “glioblastoma multiforme” – the most common and most aggressive form of primary brain cancer in adults.
The drug candidate was originally licenced from Genentech in late 2016 and entered a phase 2 clinical trial in 2018. Initial safety data was released in May this year with efficacy data currently expected to be published in the second half of 2019.
Glioblastoma is one of the most debilitating and deadly cancers, with limited treatment options that are currently effective for only a third of patients.
The newly announced trial will be conducted in combination with radiotherapy for brain-related cancers, specifically focusing on brain metastases and leptomeningeal metastases (cancers that have spread to the brain).
The first part of the trial will aim to determine the maximum tolerated dose of GDC-0084 when deployed in combination with radiotherapy.
After the appropriate dose has been determined, the second part of the study will enrol an additional 12 patients at that dose to explore preliminary signals of efficacy.
Kazia confirmed that the MSK will initiate the clinical trial of GDC-0084 in combination with radiotherapy for 18-30 patients with solid tumour brain metastases and leptomeningeal metastases that harbour a genetic alteration in the PI3K pathway.
The PI3K pathway is an intracellular signalling pathway, considered to be important in regulating the cell cycle and is thought to be directly related to cellular proliferation, cancer, and longevity.
According to scientific research, up to 30% of patients with metastatic cancer will develop secondary tumours in the brain, but while radiotherapy remains the standard of care, around 30-50% of patients will progress within one year, despite the variety of treatment options available to clinicians.
According to Kazia, there may be a neat solution to reducing cancer proliferation given results on animal models so far and its investigational new drug’s capability as a PI3K inhibitor.
In animal models of certain cancers, activation of the PI3K pathway has been shown to contribute to radiotherapy resistance. GDC-0084 is a PI3K inhibitor that can cross the blood-brain barrier, and as such, it may be able to reduce the problem of resistance to radiotherapy. The clinical trial at MSK has been developed to test precisely this hypothesis.
Given existing estimates, Kazia said the trial should take around two years to complete and will be led by MSK with Kazia tasked with providing support including study drug and a financial grant.
“Many cancers have the potential to spread to the brain, and they become very difficult to treat when they do,” said Dr James Garner, chief executive officer of Kazia.
The work being done at MSK will investigate whether GDC-0084 has the potential to enhance the effects of radiotherapy, which remains the current standard of care in most cases,” said Dr Garner.