Title: LUMOS2: Low & Anaplastic Grade Glioma Umbrella Study of Molecular Guided TherapieS  

An interventional study requiring a study-specific craniotomy and molecular testing to identify mutations. If the participant is found to have a molecular profile that matches to one of the treatment arms available, they will be consented to and screened for the matched treatment arm. If the participant does not have a molecular profile that matches a treatment arm, they will be randomised to one of the treatment arms that does not require a matched mutation. The following treatment arms are available under this protocol: Arm 1 - Paxalisib: 45mg taken orally (capsule), once daily, for a 28 day cycle. If tolerated, after cycle 1 this will increase to 60mg daily. Arm 2 - AK104: 6mg/kg as Intravenous injection, once every 2 weeks Arm 3 - Selinexor: 80mg taken orally (tablet), once daily

Eligible Population: 

1. Adults, aged 18 years and older

2. Histologically confirmed glioma, IDH-mutant, histologically grade 2 or 3 at initial diagnosis; including CDKN2A/B homozygous deleted IDH-mutant astrocytomas but not IDH-wildtype diffuse astrocytomas with any of TERT promoter mutation, EGFR amplification and/or +7/-10 copy number changes.

3. Has evidence of progressive disease.

4. Had prior treatment with radiotherapy and alkylating chemotherapy.

5. ECOG performance status 0-2.

6. No prior treatment with bevacizumab.

Substudy status: Recruiting

Registration number: ACTRN12623000096651