5G-EMERALD: Amivantamab in Malignant Brain Tumours
Trial Parameters
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.
Eligibility Criteria
Inclusion Criteria for Phase 1b: 1. Patients with histologically confirmed advanced WHO Stage IV glioblastoma (per fourth edition 2016). Per the new 2021 fifth edition of WHO Classification of Tumours of the Central Nervous System, this will include: * Glioblastoma, IDH-wildtype Grade 4 * Astrocytoma, IDH-mutant, Grade 4 (lower Grade 2/3 are not included) * Diffuse hemispheric glioma, H3 G34 mutant Grade 4 2. Patients for Phase 1 will need to have consented to the Minderoo Precision Brain Tumour Programme and have available whole genome, and transcriptome data available. 3. Patients for the relapsed cohorts will be eligible at first relapse following completion of optimal surgery, and Stupp based adjuvant chemo-radiotherapy (or equivalent). They will need to have measurable disease per Response Assessment in Neuro-Oncology (RANO) or evaluable disease. 4. Patients for the front line minimal residual disease (MRD) cohort will be eligible following completion of optimal surgery and Stupp