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

Title: Phase 2 trial of sotorasib in combination with carboplatin-pemetrexed and bevacizumab-biosimilar as first line treatment for advanced non-squamous non-small cell lung cancer with KRAS G12C mutation.

The aim of the SHERLOCK trial is to assess the activity and tolerability of sotorasib in combination with carboplatin-pemetrexed and bevacizumab-biosimilar in non-squamous metastatic NSCLC with KRAS G12C mutation.  

Eligible Population: 

KRAS G12C positive newly diagnosed, treatment naïve metastatic (Stage IV) non-squamous NSCLC or recurrent non-squamous NSCLC with no disease progression for at least 6 months following prior curative lung surgery and (neo)adjuvant chemotherapy, or prior curative concurrent chemoradiotherapy and immunotherapy maintenance, for non-resectable stage III cancer.

Substudy status: Recruiting

Registration number: ACTRN12622000973718

Title: A phase II, open-label, single-arm monotherapy trial of sulfasalazine in patients with pancreatic ductal adenocarcinoma

The aim of this MoST companion study is to assess the clinical activity of sulfasalazine in MoST patients with pancreatic ductal adenocarcinoma.

Eligible Population: 

Patients with advanced pancreatic ductal adenocarcinoma who have progressive disease following prior treatment.

Substudy status: Recruiting

Registration number: ACTRN12621001347853

Title: A Single Arm, Open-label, Phase II Signal-seeking Trial of Tiragolumab and Atezolizumab in Patients With Advanced Solid Tumours

The aim of this study is to evaluate the effect of 2 monoclonal antibodies, tiragolumab and atezolizumab, in patients with locally advanced solid cancers which cannot be removed by surgery or have spread.

Eligible Population: 

• Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumour. Non-small cell lung cancer is excluded
• Exhausted all available standard therapy or not suitable for standard therapy (including targeted therapies) for the tumour
• Sufficient and accessible tumour tissue for panel sequencing, PD-L1 and TIL testing, and tertiary objectives
• Tumour biomarker criteria predictive of immune response defined by presence of one or more of the following: 
  • Tumour Mutation Burden ≥ 10 mutations per megabase
  • Tumour and immune cell PD-L1 expression (TAP score) > 20% high or PD-L1 (CD274) amplification >6 copy number alterations
  • Tumour and immune cell PD-L1 expression (TAP score) 5-20%
  • Tumour Infiltrating Lymphocytes (TILs) (CD3+CD8+) ≥ 5%
• Prior use of approved or investigational anti-TIGIT therapy is not eligible.
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies is not eligible.

Substudy status: Recruiting

Registration number: NCT06003621