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

NCT05187624 | Completed Phase 1 FDA Drug

• 2 other identifiers: BP425732021-001197-37
• Study Type: interventional
• Target: 36
• Locations: 5 countries
• Sites: 8

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants with Adverse Events (AEs)

  Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)

• Percentage of Participants with Dose Limiting Toxicities (DLTs)

  Cycle 1 (each cycle is 21 days)

Secondary Outcomes (7)

• Serum Concentration of RO7428731

  Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)

• Percentage of Participants With RO7428731 Anti-drug Antibodies (ADAs)

  From baseline up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)

• Objective Response Rate (ORR)

  From start of study treatment up to approximately 3 years

• Disease Control Rate (DCR)

  From start of study treatment up to approximately 3 years

• Duration of Response (DOR)

  From the time of first occurrence of a documented response until the time of documented disease progression or death (death within 30 days from last study treatment) from any cause, whichever occurs first (up to approximately 3 years)

Study Arms (4)

Part I: Dose Escalation

EXPERIMENTAL

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.

Drug: RO7428731

Part II: Dose-Expansion(s)

EXPERIMENTAL

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.

Drug: RO7428731

Part III: Safety Run-in

EXPERIMENTAL

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.

Drug: RO7428731

Part IV A: Dose-Expansions Cohort

EXPERIMENTAL

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

Drug: RO7428731

Interventions

RO7428731 DRUG

Participants will receive RO7428731 as described.

Part I: Dose Escalation; Part II: Dose-Expansion(s); Part III: Safety Run-in; Part IV A: Dose-Expansions Cohort

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (8)

UCLA Neuro-Oncology Program

Los Angeles, California, 90095, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

Rigshospitalet, Onkologisk Klinik

København Ø, 2100, Denmark

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

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

Barcelona, 08035, Spain

Location

Clinica Universidad de Navarra Madrid

Madrid, 28027, Spain

Location

MeSH Terms

Conditions

Glioblastoma

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

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2021
• First Posted: January 12, 2022
• Study Start: April 5, 2022
• Primary Completion: May 14, 2025
• Study Completion: May 14, 2025
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); AU (1); ES (3); CA (1); US (2)