Clinical trial NCT05187624: A Study Evaluating the Safety, Pharmacokinetic and Anti-tumor Activity of RO7428731 in Participants With Glioblastoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Glioblastoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-01-12
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility 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 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.

Primary outcomes:
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)
measure: Percentage of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (each cycle is 21 days)
Secondary outcomes:
measure: Serum Concentration of RO7428731
timeFrame: Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)
measure: Percentage of Participants With RO7428731 Anti-drug Antibodies (ADAs)
timeFrame: From baseline up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)
measure: Objective Response Rate (ORR)
timeFrame: From start of study treatment up to approximately 3 years
measure: Disease Control Rate (DCR)
timeFrame: From start of study treatment up to approximately 3 years
measure: Duration of Response (DOR)
timeFrame: 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)
measure: Progression-free Survival (PFS)
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: From start of study treatment to the time of death from any cause (up to approximately 3 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Neuro-Oncology Program
state: California
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: København Ø
country: Denmark
facility: Rigshospitalet, Onkologisk Klinik
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra Madrid
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: