5G-EMERALD: Amivantamab in Malignant Brain Tumours

Phase 1

Recruiting

• Conditions: Malignant Primary Gliomas; Glioblastoma Multiform (Grade IV Astrocytoma); Diffuse Hemispheric Glioma, H3 G34-Mutant; Glioblastoma Multiforme (GBM)
• Interventions: Drug: Amivantamab

• Registration Number: NCT06632236
• Lead Sponsor: Institute of Cancer Research, United Kingdom

Brief 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.

Study Timeline

• Study First Submitted: 2024-10-02
• Study First Submitted QC: 2024-10-07
• Study Start: 2024-10-09
• Study First Posted: 2024-10-09
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-04
• Last Update Posted: 2024-11-06
• Primary Completion: 2026-03-05
• Study Completion: 2027-03-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental: Phase 1b	Amivantamab	The Phase 1b will evaluate the safety and tolerability of amivantamab and determine its preliminary antitumour activity when administered at the recommended Phase 2 dose (RP2D) in patients with molecularly defined malignant brain tumours.

Primary Outcome Measures

Name	Time	Method
Phase 1b - To evaluate the safety and tolerability of investigational agent in patients with malignant brain tumours	18 months	To identify the incidence, nature and severity of adverse events and laboratory abnormalities, with severity determined according to NCI CTCAE v5.0
Phase 1b - To determine the preliminary antitumour activity of the investigational agent administered at the RP2D in patients with molecularly defined malignant brain tumours	18 months	Antitumour activity will be defined on the basis of the following outcomes. If any of the following occur, patients will be considered to have clinically benefitted: For relapsed GBM: Achievement of overall response of CR or PR per Response Assessment in Neuro-Oncology (RANO) within 6 months or Free of disease progression or death at 6 months For front line unmethylated GBM (MRD): • Progression-free survival (PFS)

Secondary Outcome Measures

Name	Time	Method
Phase 1b - To identify molecular determinants of response and antitumour activity of the investigational agent in patients with molecularly selected brain tumours	18 months	Determination of biomarkers of response, including but not limited to changes in genomic, transcriptomic or immunological signatures from responders and non-responders using tumour sequencing analysis.

Trial Locations

Locations (2)

Cambridge University Hospitals; 🇬🇧 Cambridge, United Kingdom

The Royal Marsden Hospital - Drug Development Unit; 🇬🇧 Sutton, United Kingdom