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 : April 26, 2024
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Glioblastoma | Drug: RO7428731 | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 200 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | April 5, 2022 |
Estimated Primary Completion Date : | December 31, 2025 |
Estimated Study Completion Date : | December 31, 2025 |
Arm | Intervention/treatment |
---|---|
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.
|
Drug: RO7428731
Participants will receive RO7428731 as described. |
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.
|
Drug: RO7428731
Participants will receive RO7428731 as described. |
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.
|
Drug: RO7428731
Participants will receive RO7428731 as described. |
Experimental: Part IV A: Dose-Expansions Cohort
Participants with recurrent GBM will receive RO7428731, IV at specified doses and dosing schedules.
|
Drug: RO7428731
Participants will receive RO7428731 as described. |
- 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) ]
- 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) ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts 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.
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05187624
Contact: Reference Study ID Number: BP42573 https://forpatients.roche.com/ | 888-662-6728 (U.S. Only) | global-roche-genentech-trials@gene.com |
United States, California | |
UCLA Neuro-Oncology Program | Recruiting |
Los Angeles, California, United States, 90095 | |
United States, Massachusetts | |
Dana-Farber Cancer Institute | Active, not recruiting |
Boston, Massachusetts, United States, 02215 | |
United States, New York | |
Memorial Sloan Kettering Cancer Center | Recruiting |
New York, New York, United States, 11101 | |
Australia, Victoria | |
Peter MacCallum Cancer Centre; Medical Oncology | Active, not recruiting |
Melbourne, Victoria, Australia, 3000 | |
Canada, Ontario | |
Princess Margaret Cancer Center | Active, not recruiting |
Toronto, Ontario, Canada, M5G 1Z5 | |
Denmark | |
Rigshospitalet, Onkologisk Klinik; Klinisk Forskningsenhed | Recruiting |
København Ø, Denmark, 2100 | |
Germany | |
Neurologische Klinik, Universitätsklinikum Heidelberg | Withdrawn |
Heidelberg, Germany, 69120 | |
Netherlands | |
Amsterdam UMC Location VUMC | Completed |
Amsterdam, Netherlands, 1081 HV | |
Spain | |
Clinica Universitaria de Navarra | Active, not recruiting |
Pamplona, Navarra, Spain, 31008 | |
Vall d?Hebron Institute of Oncology (VHIO), Barcelona | Active, not recruiting |
Barcelona, Spain, 08035 | |
Clinica Universidad de Navarra Madrid; Servicio de Oncología | Active, not recruiting |
Madrid, Spain, 28027 | |
START Madrid-FJD, Hospital Fundacion Jimenez Diaz | Completed |
Madrid, Spain, 28040 |
Study Director: | Clinical Trials | Hoffmann-La Roche |
Responsible Party: | Hoffmann-La Roche |
ClinicalTrials.gov Identifier: | NCT05187624 |
Other Study ID Numbers: |
BP42573 2021-001197-37 ( EudraCT Number ) |
First Posted: | January 12, 2022 Key Record Dates |
Last Update Posted: | April 26, 2024 |
Last Verified: | April 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
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). |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Glioblastoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors |
Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue |