NCT06630260: 5G-RUBY

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

Recruiting now Phase 1, PHASE2 Last updated 21 January 2026

What this trial tests

Phase 1, PHASE2 trial testing Avutometinib in Glioblastoma Multiforme (GBM) in 182 participants. Currently enrolling.

Timeline

15 November 2024

Primary endpoint
30 September 2029

30 September 2030

Quick facts

Lead sponsor	Institute of Cancer Research, United Kingdom
Phase	Phase 1, PHASE2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	health services research
Enrollment	182
Start date	15 November 2024
Primary completion	30 September 2029
Estimated completion	30 September 2030
Sites	3 locations across United Kingdom

Drugs / interventions tested

• Avutometinib (AVUTOMETINIB) — full drug profile →
• Defactinib — full drug profile →
• Temozolomide (temozolomide) — full drug profile →

Conditions studied

• Glioblastoma Multiforme (GBM) — all drugs for Glioblastoma Multiforme (GBM) →
• Glioblastoma Multiform (Grade IV Astrocytoma) — all drugs for Glioblastoma Multiform (Grade IV Astrocytoma) →
• Diffuse Hemispheric Glioma, H3 G34-Mutant — all drugs for Diffuse Hemispheric Glioma, H3 G34-Mutant →
• Malignant Primary Gliomas — all drugs for Malignant Primary Gliomas →

Sponsor

Institute of Cancer Research, United Kingdom

Who can join

16 and older, any sex, with Glioblastoma Multiforme (GBM) or Glioblastoma Multiform (Grade IV Astrocytoma). Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Context-specific targeting of focal adhesion kinase in brain tumors: lessons from glioblastoma and neurofibromatosis type 2-mutant meningioma.
   Sagerer A, Eyüpoglu IY, Juratli TA, Cordes N. · · 2025 · cited 2× · PMID 41487565 · DOI 10.3389/fonc.2025.1724278
2. A comprehensive pharmacological survey across heterogeneous patient-derived glioblastoma stem cell models.
   Elliott RJR, Nagle PWK, Furqan M, Dawson JC, et al · · 2026 · cited 1× · PMID 42205701 · DOI 10.1016/j.isci.2026.115839
3. Insights into the relevance of targeting fibroblasts to control cancer.
   Boeker V, Kalluri R. · · 2025 · cited 1× · PMID 41187743 · DOI 10.1016/j.xcrm.2025.102395
4. A comprehensive pharmacological survey across heterogeneous patient-derived GBM stem cell models
   Elliott RJ, Nagle PW, Furqan M, Dawson JC, et al · · 2024 · cited 1× · DOI 10.1101/2024.11.27.625719
5. The evolution of chemotherapy in brain tumors: from historical milestones to precision medicine in glioblastoma.
   Ciafarone A, Palumbo P. · · 2026 · PMID 42222273 · DOI 10.37349/etat.2026.1002374