5G-EMERALD: Amivantamab in Malignant Brain Tumours

NCT06632236 | Recruiting Phase 1

• 1 other identifier: CCR5880
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Phase 1b - To evaluate the safety and tolerability of investigational agent in patients with malignant brain tumours

  To identify the incidence, nature and severity of adverse events and laboratory abnormalities, with severity determined according to NCI CTCAE v5.0

  18 months

• Phase 1b - To determine the preliminary antitumour activity of the investigational agent administered at the RP2D in patients with molecularly defined malignant brain tumours

  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)

  18 months

Secondary Outcomes (1)

• Phase 1b - To identify molecular determinants of response and antitumour activity of the investigational agent in patients with molecularly selected brain tumours

  18 months

Other Outcomes (3)

• Exploratory objective - To determine mechanisms of resistance to the investigational agent in patients with malignant brain tumours

  18 months

• Exploratory objective - To assess putative predictive biomarkers of the investigational agent in patients with malignant brain tumours

  18 months

• Exploratory objective - To identify putative precision therapy combinations with the potential for additive benefit

  18 months

Study Arms (1)

Experimental: Phase 1b

EXPERIMENTAL

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.

Drug: Amivantamab

Interventions

Amivantamab DRUG

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.

Also known as: JNJ-61186372

Experimental: Phase 1b

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• 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.

You may not qualify if:

• 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).
• Written (signed or dated) informed consent and be capable of co-operating with treatment and follow up.
• Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week prior to the first dose of either IMP:
• Haemoglobin (Hb): ≥ 10.0 g/dL Absolute neutrophil count: ≥ 1.5 x 10\^9/L Platelet count: ≥ 75 x 10\^9/L Coagulation: INR \<1.5 and APTT \<1.5x if not anticoagulated INR stable \> 7 days within intended therapeutic range if anticoagulated Bilirubin: ≤ 1.5 x ULN; subjects with Gilbert's syndrome can enrol if conjugated bilirubin is within normal limits.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): \< 3 x ULN Albumin: ≥ 28 g/L Creatinine: \<1.5 x ULN and creatinine clearance \> 45 ml/min as measured or calculated based on Cockcroft-Gault formula Sodium: ≥ 130 mmol/L Potassium, Calcium, Magnesium, phosphate: Within institution normal ranges (replacement is permitted) Urinary protein: \< 1+ on dipstick
• Female patients with reproductive potential must have a negative serum, or urine, pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study.
• A participant must be either of the following: a. not of childbearing potential, b. of child-bearing potential and practicing true abstinence during the entire period of the study, including up to 6 months after the last dose of the study treatment is given, or c. of childbearing potential and practicing 2 methods of contraception, including 1 highly effective user independent method and a second method, to avoid impregnating a partner or becoming pregnant, respectively. A participant must agree to continue contraception throughout the study, and for at least 6 months after the last dose of study treatment.
• Please, refer to section 4.1 of CTFG guidance "Recommendations related to contraception and pregnancy testing in clinical trials" and to section 9.6 of the Master Protocol for further details.
• Note: If the childbearing potential changes after start of the study (eg, participant of childbearing potential who is not heterosexually active becomes active, premenarchal participant experiences menarche) the participant must begin birth control, as described above.
• A participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment.
• A participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after receiving the last dose of study treatment. A participant who is sexually active with a partner of childbearing potential must agree to use a condom with spermicidal foam/gel/film/cream/suppository and their partner must also be practicing a highly effective method of contraception (ie, established use of oral, injected, or implanted hormonal methods of contraception; placement of an intrauterine device \[IUD\] or intrauterine hormone-releasing system \[IUS\]). If the participant is vasectomized, they must still use a condom (with or without spermicide) for prevention of passage of exposure through ejaculation, but their partner is not required to use contraception.
• A participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of study treatment.

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• 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

Study Sites (2)

Cambridge University Hospitals

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

The Royal Marsden Hospital - Drug Development Unit

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

amivantamab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Juanita Lopez, MD, PhD

  National Health Service, UK

  STUDY DIRECTOR

Central Study Contacts

5G Team

CONTACT

0203 437 6003; 5G-enquiries@icr.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2024
• First Posted: October 9, 2024
• Study Start: October 9, 2024
• Primary Completion: March 5, 2026
• Study Completion (Estimated): March 5, 2027
• Last Updated: April 25, 2025

Record last verified: 2025-04

Locations

GB (2)