Kazia Therapeutics Limited’s (ASX:KZA) (NASDAQ:KZIA) (FRA:NV9) GBM AGILE pivotal study (NCT03970447) - an international adaptive, multi-drug study to expedite the development of new therapies for glioblastoma - has commenced recruitment to the paxalisib arm.
Positive data from GBM AGILE is expected to support the registration of paxalisib in the US and other key markets.
The Australian oncology-focused biotechnology company had executed a definitive agreement with the Global Coalition for Adaptive Research (GCAR) in October 2020 to bring paxalisib into GBM AGILE.
The lead investigators for the paxalisib arm are Professor Ingo Mellinghoff from the Memorial Sloan Kettering Cancer Center and Dr Eudocia Q Lee from the Dana-Farber Cancer Institute.
Important commercialisation step
Kazia chief executive officer Dr James Garner said: “We are delighted to have recruitment underway, and this marks an important milestone for Kazia as we begin the new year.
“The GBM AGILE study has secured the support of leading clinicians in the glioblastoma field, and has increasingly won the confidence of regulators and industry participants, so we are excited to be a part of it.
“If the data from GBM AGILE is positive, we expect it to provide a basis for registration in glioblastoma, and it, therefore, represents an important step towards commercialisation of the drug.”
Shares have been almost 4.5% higher to $1.295 this morning and the company's market cap sits at approximately $146.4 million.
Primary endpoint overall survival
The paxalisib arm of GBM AGILE will recruit newly diagnosed patients with the unmethylated MGMT promotor, a genetic marker that denotes near-total resistance to temozolomide, the existing FDA-approved standard of care.
The study will also recruit recurrent patients, who have progressed despite treatment with temozolomide.
The adaptive design allows GBM AGILE to balance between these two patient groups according to emerging data, so it is possible for paxalisib to emerge successful in one or both populations.
The primary endpoint of GBM AGILE is overall survival, which is considered the gold standard for the evaluation of new cancer therapies, and which is the preferred approval endpoint for regulators such as the US FDA.
Total data set of up to 450 patients
This study will recruit up to 200 patients on paxalisib in total and these will be compared against a roughly similar number of patients in a control group, with patients being randomly allocated between the groups.
The total data set for paxalisib will include up to about 450 patients from GBM AGILE and the duration of paxalisib’s enrolment is initially estimated to be about 30-36 months.
However, given the adaptive design of GBM AGILE, if a definitive conclusion is evident at an earlier stage, the study will conclude at that point, with a commensurate reduction in timelines and cost.
GBM AGILE commenced operation in July 2019, with the first drug to join the study being Bayer's regorafenib, which is an approved therapy for other solid tumours.
Kazia Therapeutics’ paxalisib and Kintara Therapeutics Ltd’s (NASDAQ:KTRA) (FRA:3DM) VAL-083 commenced recruitment in January 2021.
At present, GBM AGILE is operational in over 30 centres across the US and has screened over 370 patients to date.
The study is expected to open sites in Canada, Europe, and China during 2021.
The first site to open to the paxalisib arm is the Henry Ford Cancer Institute in Detroit, under the oversight of Dr Tom Mikkelsen.
Other sites are expected to rapidly open to the paxalisib arm as they receive approval from their Institutional Review Boards.