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

The purpose of this clinical trial is to evaluate the safety and tolerability of avutometinib and defactinib and to determine the preliminary antitumour activity of avutometinib and defactinib administered at the recommended Phase 2 dose (RP2D). In the Phase 1b of this study parallel biomarker defined arms will be opened, initially in the relapsed GMB setting, enrolling 12 patients onto each arm. These patients will be treated with avutometinib and defactinib double therapy. Avutometinib will be administered orally at 3.2mg twice a week (e.g., on Monday / Thursday or Tuesday / Friday) with or without a meal. The total weekly dose of avutometinib is 6.4mg. Defactinib will be administered orally, at 200mg, twice a day within 30 min after a meal. The total daily dose of defactinib is 400mg. Once a treatment in any biomarker arm has met the "GO" decision (≥3 successes/12 patients) for relapsed GBM in Phase 1b, that arm can progress to Phase 2. The primary objective of Phase 2 is to determine the antitumour activity of investigational agents administered at the RP2D in patients with molecularly defined malignant brain tumours.

NCT Number	NCT06630260
Lead Sponsor	Institute of Cancer Research, United Kingdom Collaborators: Minderoo Foundation, Verastem, Inc., Royal Marsden NHS Foundation Trust, Cambridge University Hospitals NHS Foundation Trust, Cancer Research UK, University of Cambridge
Conditions	Glioblastoma Multiforme (GBM), Glioblastoma Multiform (Grade IV Astrocytoma), Diffuse Hemispheric Glioma, H3 G34-Mutant, Malignant Primary Gliomas
Enrollment	182 participants
Start Date	2024-11-15
Primary Completion	2029-09-30 (estimated)
Study Completion	2030-09-30 (estimated)
Updated on ClinicalTrials.gov	2026-01-21