OncoMatch/Clinical Trials/NCT06630260
5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours
Is NCT06630260 recruiting? Yes, currently enrolling (Jun 2026). This Phase 1/2 trial studies multiple treatments including Avutometinib and Defactinib for glioblastoma multiforme (gbm).
Treatment: Avutometinib · Defactinib · Temozolomide — 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.
Check if I qualifyExtracted eligibility criteria
Treatments studied
Targeted therapy
Chemotherapy
Cancer type
Glioblastoma
Biomarker criteria
Required: IDH1 wild-type
Glioblastoma, IDH-wildtype Grade 4
Required: IDH1 mutation
Astrocytoma, IDH-mutant, Grade 4
Required: H3F3A (H3 K27M) G34 mutation
Diffuse hemispheric glioma, H3 G34 mutant Grade 4
Disease stage
Required: Stage IV
Grade: 4 (who)
Performance status
WHO 0–1
Demographics
Prior therapy
Must have received: surgery — frontline
completion of optimal surgery
Must have received: Stupp based adjuvant chemoradiotherapy — frontline
Stupp based adjuvant chemo-radiotherapy (or equivalent)
Cannot have received: cytotoxic chemotherapy
Exception: allowed if >2 weeks since last dose (6 weeks for nitrosoureas)
Cytotoxic chemotherapy during the prior 2 weeks or 6 weeks for nitrosoureas
Cannot have received: bevacizumab (bevacizumab)
Exception: allowed if >6 weeks since last dose
Bevacizumab during the prior 6 weeks
Cannot have received: immune checkpoint inhibitor
Prior immune checkpoint inhibitor therapy or vaccine therapy is not permitted
Cannot have received: vaccine therapy
Prior immune checkpoint inhibitor therapy or vaccine therapy is not permitted
Cannot have received: BRAF inhibitor
Prior use of BRAF or MEK inhibitors is not permitted
Cannot have received: MEK inhibitor
Prior use of BRAF or MEK inhibitors is not permitted
Lab requirements
Blood counts
Haemoglobin (Hb): ≥ 9.0 g/dL; Absolute neutrophil count: ≥1.5 x 10^9/L; Platelet count: ≥100 x 10^9/L; Coagulation: INR <1.5 and APTT <1.5x if not anticoagulated, INR stable > 7 days within intended therapeutic range if anticoagulated
Kidney function
Creatinine: <1.5 x ULN; Sodium: ≥130 mmol/L; Potassium, Calcium, Magnesium, phosphate: Within institution normal ranges (replacement is permitted); Urinary protein: < 1+ on dipstick
Liver function
Bilirubin: Within institution normal ranges; ALT and AST: <3 x ULN; Albumin: ≥ 28 g/dL
Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week prior to the first dose of either IMP
Structured fields extracted by AI. May contain errors — verify against the official protocol.
Frequently asked questions
Is NCT06630260 currently recruiting?
Yes, this trial is currently recruiting patients.
Are there prior therapy exclusions?
Yes. Prior cytotoxic chemotherapy, bevacizumab, immune checkpoint inhibitor disqualifies patients from enrollment.
Does this trial require IDH1?
Yes, IDH1 wild-type is a required biomarker for enrollment.
Does this trial require IDH1?
Yes, IDH1 mutation is a required biomarker for enrollment.
Does this trial require H3F3A?
Yes, H3F3A G34 mutation is a required biomarker for enrollment.
What disease stage is eligible?
Stage IV is required.
Could you qualify for this trial?
Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.
Check if I qualifyRelated pages