Phase 12 Study of Avutometinib and Defactinib with or without Temozolomide for Adults with High Grade Malignant Brain Tumors

What this Trial Is About

Researchers are evaluating the safety, tolerability, and preliminary antitumour activity of two investigational drugs, avutometinib and defactinib, in patients with high grade malignant brain tumours, including glioblastoma GBM. This Phase 12 clinical trial uses biomarker-guided approaches to target specific molecular subtypes of brain tumours. The study is part of the Minderoo 5G platform and includes patients with relapsed or frontline minimal residual disease MRD settings. In Phase 1b, patients with relapsed GBM will receive oral avutometinib at a dose of 3.2 mg twice weekly and defactinib at 200 mg twice daily after meals, aiming for a total weekly dose of 6.4 mg and daily dose of 400 mg respectively. Phase 2 will test the antitumour activity of these drugs given at the recommended dose, either as a doublet or combined with temozolomide, depending on earlier results. Treatment will be given in molecularly defined biomarker arms, with decisions guided by safety and efficacy data. Participants will undergo assessments for safety, tolerability, and tumour response over 9 to 12 months. Molecular profiling will help identify response markers, and quality of life will be monitored during Phase 2. Patients must consent to genomic testing and will be followed regularly with clinical evaluations. The study includes rigorous monitoring for side effects and disease progression, with a total participation duration aligned with treatment phases and follow-up.

5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours