Results for GDC-0084, an investigational drug being being developed by Australian- based and oncology-focused Kazia Therapeutics, were presented during the annual meeting of the Society for Neuro-Oncology (SNO), held in in New Orleans, LA November 16 – 18, 2018.
The investigational agent is currently in human trials for the treatment of patients with glioblastoma, the most common and most aggressive form of primary brain cancer in adults, and several other forms of brain cancer.
GDC-0084 is a small molecule inhibitor of the PI3K / AKT / mTOR pathway licensed from Genentech in late 2016. The agent entered a phase II clinical trial in March 2018. Initial data is expected in early calendar 2019. GDC-0084 was granted orphan designation for glioblastoma by the United States Food and Drug Administration (FDA) in February 2018.
Phase II trials
A Phase II clinical trial of GDC-0084, an investigational agent for the treatment of patients with glioblastoma, show promissing results. Clinical trials for the drug ar currently enrolling patients in investigator-initiated clinical collaborations at St. Jude Children’s Research Hospital in diffuse intrinsic pontine glioma (DIPG), and with Dana-Farber Cancer Institute in breast cancer brain metastases (BCBM).
Researchers presented the latest updated in a ‘trial in progress’ poster.
“We are delighted with progress across the GDC-0084 program. Our own study in glioblastoma is off to an excellent start, and we are very pleased to now also be working with two top-tier research hospitals to explore additional uses of the drug in other forms of brain cancer. The hard work that has been undertaken over the past twelve to eighteen months is now paying off, which sets the company up for several important and value-driving data read-outs from the GDC-0084 program during calendar 2019,” said James Garner MD, Chief Executive Officer and Managing Director of Kazia Therapeutics.
“The PI3K inhibitor class has seen some dramatic developments in the past six months. We were excited to see FDA approve Copiktra (duvelisib) from Verastem in October 2018, bringing the number of FDA-approved PI3K inhibitors to three,” he added.
“The recent European Society for Medical Oncology (ESMO) meeting also saw promising data presented from Novartis for their PI3K inhibitor, alpelisib, in certain forms of breast cancer. It is clear that this class of drugs is well-established and well-proven. However, GDC-0084 remains the only PI3K inhibitor in mainstream development that is able to cross the blood-brain barrier, and this gives it a unique advantage in brain cancer,” Garner observed.
Phase II Clinical Trial
All seven participating centers are fully open to recruitment. To date, the first cohort of three patients has been enrolled and are currently receiving treatment. If the first cohort is able to complete treatment without experiencing significant toxicity, a second cohort will be enrolled at a higher dose.
A number of potential patients have already been identified for the second cohort and are undergoing pre-screening. Once the maximum tolerated dose (MTD) has been established in this first part of the trial, the remainder of the study will proceed at that dose.
The researchers noted that trial recruitment has exceeded expectations, and the study remains on track to report initial data early in calendar 2019.
Kazia is also supporting two leading U.S.-based hospitals to explore the potential use of GDC-0084 in other forms of brain cancer.
- St Jude Children’s Research Hospital in Memphis, TN has started a Phase I human trial of GDC-0084 in children with diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas(NCT03696355). Pediatric high-grade gliomas are highly aggressive and treatment options are limited. This study is designed to enable a preliminary assessment of the antitumor activity of single- agent GDC-0084, in the hope of enabling rational combination therapy with systemic therapy and/or radiation therapy (RT) in this patient population, which is in desperate need of therapeutic advances. 
- Dana-Farber Cancer Institute (DFCI) in Boston, MA is establishing a Phase II human trial of GDC-0084 in women with breast cancer brain metastases (BCBM), which is breast cancer that has spread to the brain. This study is expected to start recruitment in early 2019, pending approval by the Institutional Review Board at DFCI.
 Study of GDC-0084 in Pediatric Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma or Diffuse Midline Gliomas – NCT03696355.
Last Editorial Review: November 18, 2018
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