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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05187624
Recruitment Status : Recruiting
First Posted : January 12, 2022
Last Update Posted : August 3, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE December 18, 2021
First Posted Date  ICMJE January 12, 2022
Last Update Posted Date August 3, 2022
Actual Study Start Date  ICMJE April 5, 2022
Estimated Primary Completion Date February 6, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2022)
  • 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) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2022)
  • Maximum Plasma Concentration (Cmax) of RO7428731 [ Time Frame: Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months) ]
  • Time to Maximum Plasma Concentration (Tmax) of RO7428731 [ Time Frame: Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months) ]
  • Minimum Observed Serum Concentration (Cmin) of RO7428731 [ Time Frame: Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months) ]
  • Clearance (CL) of RO7428731 [ Time Frame: Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months) ]
  • Half-life (t1/2) of RO7428731 [ Time Frame: Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months) ]
  • Volume of Distribution at Steady State (Vss) of RO7428731 [ Time Frame: Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months) ]
  • Area Under the Plasma Concentration-Time Curve (AUC) 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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Safety, Pharmacokinetic and Anti-tumor Activity of RO7428731 in Participants With Glioblastoma
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE Drug: RO7428731
Participants will receive RO7428731 as described.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: RO7428731
  • 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.
    Intervention: Drug: RO7428731
  • 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.
    Intervention: Drug: RO7428731
  • Experimental: Part IV A: Dose-Expansions Cohort
    Participants with recurrent GBM will receive RO7428731, IV at specified doses and dosing schedules.
    Intervention: Drug: RO7428731
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 7, 2022)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 6, 2025
Estimated Primary Completion Date February 6, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 the Consortium to Inform Molecular and Practical Approaches to Central Nervous System Tumor Taxonomy (cIMPACT) NOW 6 criteria
  • 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 O6-methylguanine-DNA methyltransferase (MGMT) promotor status based on local assessment
  • Participants must have completed standard of care therapy for newly diagnosed disease, including surgical resection and adjuvant radiotherapy with or without concomitant temozolomide.

Inclusion criteria for Part III and Part IV only:

  • Documented first or second recurrence of GBM
  • At least one measurable GBM lesion as per 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 must be the only tumor-directed treatment that the participant has received for GBM.

Exclusion criteria for Part III and Part IV 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number: BP42573 https://forpatients.roche.com/ 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com
Listed Location Countries  ICMJE Australia,   Canada,   Denmark,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05187624
Other Study ID Numbers  ICMJE BP42573
2021-001197-37 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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).
Current Responsible Party Hoffmann-La Roche
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hoffmann-La Roche
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP