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

Sponsor
Institute of Cancer Research, United Kingdom
Study ID
NCT06630260
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

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

Eligibility Criteria

Sex
ALL
Age
16 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Avutometinib — DRUG
    Supplied as 0.8mg capsules.
  • Defactinib — DRUG
    Supplied as 200mg tablets.
  • Temozolomide — DRUG
    Temozolomide will be supplied as 5, 20, 100, 140, 180 or 250 mg hard capsules.

Study Details

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.

Key Dates

Start date
Nov 15, 2024
Status verified
Jan 2026
Primary completion
Sep 30, 2029
Completion
Sep 30, 2030

Study Design

Enrollment
182 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH

Arms

  • Experimental: Phase 1b
    The Phase 1b will evaluate the safety and tolerability of combination of avutometinib and defactinib and determine its preliminary antitumour activity when administered at the recommended Phase 2 dose (RP2D) in patients with molecularly defined malignant brain tumours.
  • Experimental: Phase 2
    The Phase 2 part of the study will determine the antitumour activity of investigational agents administered at the RP2D in patients with molecularly defined malignant brain tumours. Avutometinib and defactinib may be administered in combination with temozolomide (TMZ).

Primary Outcome Measure

Phase 1b - To evaluate the safety and tolerability of investigational agent in patients with malignant brain tumours [ Time Frame: 12 months ]

Central Contacts

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