A Study Evaluating the Safety, Pharmacokinetic and Anti-tumor Activity of RO7428731 in Participants With Glioblastoma
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Maximum Plasma Concentration (Cmax) of RO7428731 [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 [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 [Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)]
- Clearance (CL) of RO7428731 [Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)]
- Half-life (t1/2) of RO7428731 [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 [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 [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) [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]
- Disease Control Rate (DCR) [From start of study treatment 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)]
- Overall Survival (OS) [From start of study treatment to the time of death from any cause (up to approximately 3 years)]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peter MacCallum Cancer Centre; Medical Oncology | Melbourne | Victoria | Australia | 3000 |
| 2 | Princess Margaret Cancer Center | Toronto | Ontario | Canada | M5G 1Z5 |
| 3 | Rigshospitalet, Onkologisk Klinik; Klinisk Forskningsenhed | København Ø | Denmark | 2100 | |
| 4 | Clinica Universitaria de Navarra | Pamplona | Navarra | Spain | 31008 |
| 5 | Vall d´Hebron Institute of Oncology (VHIO), Barcelona | Barcelona | Spain | 08035 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BP42573
- 2021-001197-37