NCT06632236

5G-EMERALD: Amivantamab in Malignant Brain Tumours

5G-EMERALD: A Phase 1 Trial of Amivantamab in High Grade Malignant Brain Tumours Within the 5G Platform

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Institute of Cancer Research, United Kingdom · Academic / Other
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this clinical trial is to evaluate the safety and tolerability of amivantamab and to determine the preliminary antitumour activity of amivantamab administered at the recommended Phase 2 dose (RP2D). In the Phase 1b of this study a biomarker defined arm will be opened, initially in the relapsed GMB setting, enrolling 12 patients. These patients will be treated with amivantamab monotherapy. Amivantamab will be administered intravenously (IV) weekly for the first 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity. The first dose will be given as a split infusion, 350 mg IV over 4 hours on cycle 1 day 1 and 1400 mg IV over 6 hours on cycle 1 day 2. Subsequent infusions are given at a dose of 1750 mg IV over 2-5 hours in cycle 1 and between 2-3 hours from cycle 2 onwards if the first dose was well-tolerated with no significant toxicity. Progression to Phase 2 is dependent on emergent data and funding.

Detailed description

The clinical trial will start in Phase 1b (proof of concept of hypothesis-driven biomarker-guided therapies). This is a study within Minderoo 5G: A Next Generation AGile Genomically Guided Glioma Modular Platform for proof-of-concept molecular hypothesis testing in patients with high grade malignant brain tumours. 5G-EMERALD is a Bayesian multi-centre, multi-arm, open-label, adaptive, seamless Phase 1 trial of amivantamab for patients with high grade malignant brain tumours. 5G-EMERALD will recruit patients with glioblastoma (GBM) into one molecularly-defined biomarker arm of patients who have tumours that harbour: • EGFR amplification (high copy number) The above mentioned arm, within Phase 1, will have robust GO/ADAPT decision points, reviewed by the Safety Review Committee (SRC) to allow for both agility and clear direction for next steps. A 2-stage Bayesian adaptive design will be performed to assess preliminary efficacy. In the Phase 1b of this study a biomarker defined arm will be opened, initially in the relapsed GBM setting, enrolling 12 patients onto each arm. These patients will be treated with amivantamab. Amivantamab will be administered intravenously (IV) weekly for the first 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity.

Conditions

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

Interventions

Type	Name	Description
DRUG	Amivantamab	Amivantamab will be supplied in single-use 350 mg injectable solution, provided as a 7 ml per glass vial (50mg/ml), intended for IV infusion.

Timeline

• Start date: 2024-10-09
• Primary completion: 2026-03-05
• Completion: 2027-03-05
• First posted: 2024-10-09
• Last updated: 2025-04-25

Locations

2 sites across 1 country: United Kingdom