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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05187624




Registration number
NCT05187624
Ethics application status
Date submitted
18/12/2021
Date registered
12/01/2022

Titles & IDs
Public title
A Study Evaluating the Safety, Pharmacokinetic and Anti-tumor Activity of RO7428731 in Participants With Glioblastoma
Scientific 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
Secondary ID [1] 0 0
2021-001197-37
Secondary ID [2] 0 0
BP42573
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RO7428731

Experimental: 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.

Experimental: 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.

Experimental: 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.

Experimental: Part IV A: Dose-Expansions Cohort - Participants with recurrent GBM will receive RO7428731, IV at specified doses and dosing schedules.


Treatment: Drugs: RO7428731
Participants will receive RO7428731 as described.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [1] 0 0
Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)
Primary outcome [2] 0 0
Percentage of Participants with Dose Limiting Toxicities (DLTs)
Timepoint [2] 0 0
Cycle 1 (each cycle is 21 days)
Secondary outcome [1] 0 0
Serum Concentration of RO7428731
Timepoint [1] 0 0
Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)
Secondary outcome [2] 0 0
Percentage of Participants With RO7428731 Anti-drug Antibodies (ADAs)
Timepoint [2] 0 0
From baseline up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)
Secondary outcome [3] 0 0
Objective Response Rate (ORR)
Timepoint [3] 0 0
From start of study treatment up to approximately 3 years
Secondary outcome [4] 0 0
Disease Control Rate (DCR)
Timepoint [4] 0 0
From start of study treatment up to approximately 3 years
Secondary outcome [5] 0 0
Duration of Response (DOR)
Timepoint [5] 0 0
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 outcome [6] 0 0
Progression-free Survival (PFS)
Timepoint [6] 0 0
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 outcome [7] 0 0
Overall Survival (OS)
Timepoint [7] 0 0
From start of study treatment to the time of death from any cause (up to approximately 3 years)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre; Medical Oncology - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Denmark
State/province [5] 0 0
København Ø
Country [6] 0 0
Netherlands
State/province [6] 0 0
Amsterdam
Country [7] 0 0
Spain
State/province [7] 0 0
Navarra
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
Spain
State/province [9] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05187624