Glioblastoma
Conditions
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).
Interventions
DRUGRO7428731
Participants will receive RO7428731 as described.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Overall Survival (OS) | From start of study treatment to the time of death from any cause (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) |
| 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) |
| Disease Control Rate (DCR) | From start of study treatment up to approximately 3 years |
| Serum Concentration of RO7428731 | Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months) |
Countries
Australia, Canada, Denmark, Spain, United States
Outcome results
None listed