On June 8, 2023 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported that it is supporting the University of Sydney on a molecularly-guided phase II clinical study to examine paxalisib in adult patients with recurrent/progressive isocitrate dehydrogenase (IDH) mutant grade 2 and 3 glioma (G2/3 gliomas) (Press release, Kazia Therapeutics, JUN 8, 2023, View Source;3-glioma-301845484.html [SID1234632598]).
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The study, named LUMOS2, will be sponsored by the University of Sydney, and coordinated by NHMRC Clinical Trials Centre, University of Sydney, in collaboration with COGNO (Co-Operative Trials Group for Neuro-Oncology).
The study team will be led by Professor Hui Gan, Co-Director, Centre for Research Excellence in Brain Cancer and research clinician at the Olivia Newton-John Cancer Research Institute in Melbourne, VIC, who specializes in the investigation of novel therapies for brain cancer.
Key Points
The LUMOS2 study aims to investigate paxalisib and other targeted therapies in adult patients with grade 2 or 3 IDH-mutant gliomas. Paxalisib is already the subject of several studies in high-grade glioma, a category which includes diseases such as glioblastoma and Diffuse Intrinsic Pontine Glioma (DIPG).
Grade 2 and 3 gliomas represent a substantial unmet clinical need, with recurrent patients having a poor prognosis that is comparable to glioblastoma. The glioma patient population has been the subject of increasing focus for drug development companies, including Day One Biopharmaceuticals (NASDAQ: DAWN), Servier and Novartis (NYSE: NVS).
LUMOS2, an umbrella study with multiple arms, is expected to enroll up to 76 patients and will be a multi-centre study at several Australian sites, with the potential to expand internationally.
The study is funded by the Australian Government, through a Medical Research Future Fund (MRFF) grant, with Kazia’s contribution consisting of study drug supply and in-kind support.
"We are delighted to have paxalisib as one of the interventional arms in the LUMOS 2 study," commented Professor Hui Gan, lead investigator on the study. "Relapsed IDH mutant gliomas are an important area of unmet need in brain cancer, and the LUMOS2 study builds on early phase II data seen with paxalisib in this population. LUMOS2 will complement some of the ongoing work with paxalisib evaluating the efficacy of the drug in high-grade gliomas, and we expect the study to add substantially to our understanding of this investigational drug in brain cancer."
Low Grade Glioma
Gliomas are the most common form of primary brain cancer, accounting approximately for a third of malignancies that originate in the brain. They are sub-classified into oligodendrogliomas or astrocytomas, according their morphology and the presence of characteristic molecular alterations. Grade 2 and 3 IDH mutant astrocytomas are collectively the next largest group after glioblastoma, comprising just over 20% of gliomas (with a rate of 0.016 per 2000 patients).
High Grade Gliomas (HGGs) include diseases such as glioblastoma (grade 4 glioma), and diffuse midline gliomas such as DIPG. Paxalisib has shown evidence of clinical activity in several forms of HGG.
G2/3 gliomas remain an area of significant unmet need, with very few FDA-approved therapies and limited response to repeated courses of radiotherapy. Whilst the disease is often well-controlled after first-line standard of care therapies, patients with recurrent disease unfortunately have a prognosis comparable to glioblastoma, and current treatment options may offer only limited effectiveness for these patients.
Clinical Study Design
LUMOS2 is a prospective, multi-centre, open-label, multi-arm, phase II, biomarker-directed, signal-seeking, umbrella clinical trial. Adults with progressive grade 2/3, IDH-mutant glioma at recurrence after prior treatment with radiotherapy and alkylating chemotherapy who are eligible and willing to undergo tumour resection in consultation with their treating physician will undergo molecular profiling, the results of which will serve as a recommendation to be assigned to a treatment arm. The primary objective of the study is to determine progression-free survival at six months (PFS6) with overall survival, response rate and health-related quality of life as secondary endpoints.