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

Glioblastoma Clinical Trial

Official title:

An Open-label, Multicenter, Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Activity of RO7428731 in Participants With Glioblastoma Expressing Mutant Epidermal Growth Factor Receptor Variant III

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05187624
• Other study ID #: BP42573
• Secondary ID: 2021-001197-37
• Status: Recruiting
• Phase: Phase 1
• Start date: April 5, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BP42573 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Inclusion criteria for all participants:

• 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.

Inclusion criteria for Part I and Part II only:

• 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.

Inclusion criteria for Part III and Part IV A only:

• 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:

Exclusion criteria for all participants:

• 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.

Exclusion criteria for Part I and Part II only:

• 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.

Exclusion criteria for Part III and Part IV A only:

• 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.

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• RO7428731
Participants will receive RO7428731 as described.

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre; Medical Oncology	Melbourne	Victoria
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Denmark	Rigshospitalet, Onkologisk Klinik; Klinisk Forskningsenhed	København Ø
Germany	Neurologische Klinik, Universitätsklinikum Heidelberg	Heidelberg
Netherlands	Amsterdam UMC Location VUMC	Amsterdam
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Clinica Universidad de Navarra Madrid; Servicio de Oncología	Madrid
Spain	START Madrid-FJD, Hospital Fundacion Jimenez Diaz	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	UCLA Neuro-Oncology Program	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Denmark,  Germany,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Percentage of Participants with Dose Limiting Toxicities (DLTs)		Cycle 1 (each cycle is 21 days)
Secondary	Serum Concentration of RO7428731		Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)
Secondary	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)
Secondary	Objective Response Rate (ORR)		From start of study treatment up to approximately 3 years
Secondary	Disease Control Rate (DCR)		From start of study treatment up to approximately 3 years
Secondary	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)
Secondary	Progression-free Survival (PFS)		From start of study treatment to the first occurrence of documented disease progression or death from any cause, whichever occurs first (up to approximately 3 years)
Secondary	Overall Survival (OS)		From start of study treatment to the time of death from any cause (up to approximately 3 years)