On January 7, 2021 Kazia Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian oncology-focused biotechnology company, reported that the GBM AGILE pivotal study (NCT03970447) has commenced recruitment to the paxalisib arm (Press release, Kazia Therapeutics, JAN 7, 2021, View Source [SID1234573609]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Key Points

GBM AGILE is an international adaptive, multi-drug study, designed to expedite the development of new therapies for glioblastoma

Kazia executed a definitive agreement with the Global Coalition for Adaptive Research (GCAR) in October 2020 to bring paxalisib into GBM AGILE

Lead investigators for the paxalisib arm are Professor Ingo Mellinghoff (Memorial Sloan Kettering Cancer Center) and Dr Eudocia Q Lee (Dana-Farber Cancer Institute)

Positive data from GBM AGILE is expected to support registration of paxalisib in the US and other key markets

Kazia CEO, Dr James Garner, commented, "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.

Clinical Trial Design

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. In addition, the study will 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.

The 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 therefore include up to approximately 450 patients from GBM AGILE. The duration of paxalisib’s enrolment is initially estimated to be approximately 30-36 months. However, the adaptive design of GBM AGILE means that 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.

Further information was provided in Kazia’s announcement to the ASX on 16 October 2020.

Operational Update on GBM AGILE

GBM AGILE commenced operation in July 2019. The first drug to join the study was regorafenib (Bayer), which is an approved therapy for other solid tumours. Kazia Therapeutics’ paxalisib and Kintara Therapeutics’ VAL-083 commenced recruitment in January 2021.

At present, GBM AGILE is operational in over 30 centres across the United States and has screened over 370 patients to date. The study is expected to open sites in Canada, Europe, and China during CY2021.

The first site to open to the paxalisib arm is the Henry Ford Cancer Institute in Detroit, MI, under the oversight of Dr Tom Mikkelsen. It is expected that other sites will rapidly open to the paxalisib arm as they receive approval from their Institutional Review Boards.

Paxalisib Clinical Program

GBM AGILE is one of eight ongoing clinical trials of paxalisib in brain cancer.