GlioblastomaPhase 1NCT05187624
A Study Evaluating the Safety, Pharmacokinetic and Anti-tumor Activity of RO7428731 in Participants With Glioblastoma
A Phase 1 study testing RO7428731 in people with Glioblastoma, run by Hoffmann-La Roche at 8 sites in 5 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- RO7428731
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 8 sitesin 5 countries
- Study dates
- 5 Apr 2022to 14 May 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
8 sites in 5 countries.
8 sites in 5 countries
Spain3 sites
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
Barcelona, 08035
Clinica Universidad de Navarra Madrid
Madrid, 28027
Clinica Universitaria de Navarra
Pamplona, Navarre, 31008
United States2 sites
UCLA Neuro-Oncology Program
Los Angeles, California, 90095
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
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
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
- Being tested
- RO7428731
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO7428731Drug
Participants will receive RO7428731 as described.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: RO7428731 |
| Part IV A: Dose-Expansions Cohort | Experimental | Participants with recurrent GBM will receive RO7428731, IV at specified doses and dosing schedules. Receives: Drug: RO7428731 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with Adverse Events (AEs)
Measured: 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)
Measured: Cycle 1 (each cycle is 21 days)
Secondary outcomes (7)
Serum Concentration of RO7428731
Measured: 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)
Measured: From baseline up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)
Objective Response Rate (ORR)
Measured: From start of study treatment up to approximately 3 years
Disease Control Rate (DCR)
Measured: From start of study treatment up to approximately 3 years
Duration of Response (DOR)
Measured: 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)
Measured: 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)
Overall Survival (OS)
Measured: From start of study treatment to the time of death from any cause (up to approximately 3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2022
- Study start5 Apr 2022
- Primary completion14 May 2025
- Study completion14 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05187624
- Sponsor's protocol ID
- BP42573
- Other IDs
- 2021-001197-37
- Status last verified
- May 2025
- First submitted
- 18 Dec 2021
- Last updated
- 22 May 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05187624
- Acronym / sponsor ID
- BP42573
- Conditions
- Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 5 Apr 2022 (actual)
- Primary completion
- 14 May 2025 (actual)
- Study completion
- 14 May 2025 (actual)
- First posted
- 12 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part I: Dose Escalation | Experimental | Drug: RO7428731Participants 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. |
| Part II: Dose-Expansion(s) | Experimental | Drug: RO7428731Participants 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. |
| Part III: Safety Run-in | Experimental | Drug: RO7428731Participants 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. |
| Part IV A: Dose-Expansions Cohort | Experimental | Drug: RO7428731Participants with recurrent GBM will receive RO7428731, IV at specified doses and dosing schedules. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RO7428731Participants will receive RO7428731 as described. | Drug | Part I: Dose Escalation, Part II: Dose-Expansion(s), Part III: Safety Run-in, Part IV A: Dose-Expansions Cohort |
Primary outcome
Percentage of Participants with Adverse Events (AEs)
Time frame: 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)
Time frame: Cycle 1 (each cycle is 21 days)
7 secondary outcomes
Serum Concentration of RO7428731
Time frame: 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)
Time frame: From baseline up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)
Objective Response Rate (ORR)
Time frame: From start of study treatment up to approximately 3 years
Disease Control Rate (DCR)
Time frame: From start of study treatment up to approximately 3 years
Duration of Response (DOR)
Time frame: 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)
Time frame: 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)
Overall Survival (OS)
Time frame: From start of study treatment to the time of death from any cause (up to approximately 3 years)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
8 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RO7428731 in people with Glioblastoma, run by Hoffmann-La Roche at 8 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Spain, United States, Australia, Canada, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants with Adverse Events (AEs) (time frame: Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2025.