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.
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
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.
16 years or over.
Life expectancy of at least 12 weeks.
World Health Organisation (WHO) performance status of 0-1.
Neurologically stable (e.g., without a progression of neurological symptoms or requiring escalating doses of systemic steroid therapy within the last week).
Institute of Cancer Research, United Kingdom
Lead sponsor
Royal Marsden NHS Foundation Trust
Collaborator
Cambridge University Hospitals NHS Foundation Trust
Collaborator
Janssen Pharmaceutica N.V., Belgium
Collaborator
Cancer Research UK
Collaborator
Minderoo Foundation
Collaborator
University of Cambridge
Collaborator