A Study Evaluating the Safety, Pharmacokinetic and Anti-tumor Activity of RO7428731 in Participants With Glioblastoma

NCT ID: NCT05187624

Last Updated: 2025-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-05
• Study Completion Date: 2025-05-14

Brief Summary

This is an open-label, multicenter study to assess safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and preliminary efficacy of RO7428731 administered as a monotherapy in participants with newly diagnosed or recurrent epidermal growth factor receptor variant III (EGFRvIII)-positive glioblastoma (GBM).

Conditions

Glioblastoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part I: Dose Escalation

Participants with newly diagnosed GBM will receive RO7428731, intravenously (IV), up to one year or until disease progression, withdrawal of consent, unacceptable toxicity, or death, whichever occurs first.

Group Type: EXPERIMENTAL

RO7428731

Intervention Type: DRUG

Participants will receive RO7428731 as described.

Part II: Dose-Expansion(s)

Participants with newly diagnosed GBM will receive RO7428731, IV, in maximum of two dose expansion cohorts at a dose(s) not exceeding the maximum tolerated dose (MTD) established in Part I.

Group Type: EXPERIMENTAL

RO7428731

Intervention Type: DRUG

Participants will receive RO7428731 as described.

Part III: Safety Run-in

Participants with recurrent GBM will receive RO7428731, IV in a dosing schedule determined in Part I. At the end of the Safety Run-in period, a decision will be made as to whether to open the Dose-Expansion Cohort Part IVA or open a second Safety Run-in Cohort at a lower dose.

Group Type: EXPERIMENTAL

RO7428731

Intervention Type: DRUG

Participants will receive RO7428731 as described.

Part IV A: Dose-Expansions Cohort

Participants with recurrent GBM will receive RO7428731, IV at specified doses and dosing schedules.

Group Type: EXPERIMENTAL

RO7428731

Intervention Type: DRUG

Participants will receive RO7428731 as described.

Interventions

RO7428731

Participants will receive RO7428731 as described.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Life expectancy of greater than or equal to 12 weeks, in the opinion of the Investigator
• Diagnosis of GBM based on World Health Organization (WHO) classification of central nervous system (CNS) tumors, 5th edition
• Participants must have confirmed EGFRvIII-expression
• Karnofsky Performance Status (KPS) Score of >=70%
• Adequate organ functions prior to start of study treatment
• Willingness to abide by contraceptive measures for the duration of the study.

• Participants whose tumors have an unmethylated (Part I and Part II) or methylated (Part I only) O6-methylguanine-DNA methyltransferase (MGMT) promotor status based on local assessment
• Participants (in Part I): Adult participants with newly diagnosed EGFRvIII-positive GBM with unmethylated MGMT promotor status who have completed standard of care therapy with surgical resection and adjuvant radiotherapy with or without concomitant temozolomide. Participants are allowed to have received any number of cycles of temozolomide maintenance. Adult participants with newly diagnosed EGFRvIII-positive GBM with methylated MGMT promotor status who have completed standard of care with surgical resection and adjuvant radiotherapy with concomitant and maintenance temozolomide or discontinued temozolomide maintenance due to reasons other than progressive disease.
• Participants (in Part II): Adult participants with newly diagnosed EGFRvIII-positive GBM with unmethylated MGMT promotor status who have completed standard of care therapy with surgical resection and adjuvant radiotherapy with or without concomitant temozolomide.

• Documented first or second recurrence of GBM
• At least one measurable GBM lesion as per Response Assessment in Neuro-Oncology (RANO) criteria prior to initiation of study treatment.

Exclusion Criteria

• Participants with infratentorial tumors and tumors primarily located in or close to critical structures (e.g., brain stem)
• Presence of extracranial metastatic or leptomeningeal disease
• Known hypersensitivity to immunoglobulins or to any other component of the investigational medicinal product formulation
• Active bleeding or pathological condition that carries a high risk of bleeding, including inherited and acquired coagulopathies
• Participants unable to undergo an MRI with contrast.

• Recurrent malignant gliomas
• Any prior anti-tumor treatment for GBM: tumor resection, adjuvant radiotherapy with or without concomitant temozolomide and temozolomide maintenance (Part I only) must be the only tumor-directed treatment that the participant has received for GBM.

• More than two recurrences of GBM
• Prior anti-EGFRvIII-targeting agents (including vaccines), anti-angiogenic therapy, and/or gene therapy for the treatment of GBM and gliomas.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

UCLA Neuro-Oncology Program

Los Angeles, California, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Rigshospitalet, Onkologisk Klinik

København Ø, , Denmark

Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, , Spain

Clinica Universidad de Navarra Madrid

Madrid, , Spain

Countries

United States; Australia; Canada; Denmark; Spain

Other Identifiers

2021-001197-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BP42573

Identifier Type: -

Identifier Source: org_study_id