JOURNAL ONKOLOGIE – STUDIE

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

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05187624

Studienbeginn:
April 2022

Letztes Update:
26.04.2024

Wirkstoff:
RO7428731

Indikation (Clinical Trials):
Glioblastoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Hoffmann-La Roche

Collaborator:
-

Studienleiter

Clinical Trials
Study Director
Hoffmann-La Roche

Kontakt

Reference Study ID Number: BP42573 https://forpatients.roche.com/
Kontakt:
Phone: 888-662-6728 (U.S. Only)
E-Mail: global-roche-genentech-trials@gene.com» Kontaktdaten anzeigen

Studienlocations
(3 von 12)

Neurologische Klinik, Universitätsklinikum Heidelberg
69120 Heidelberg
(Baden-Württemberg)
GermanyZurückgezogen» Google-Maps

UCLA Neuro-Oncology Program
90095 Los Angeles
United StatesRekrutierend» Google-Maps

Dana-Farber Cancer Institute
02215 Boston
United StatesAktiv, nicht rekrutierend» Google-Maps

Memorial Sloan Kettering Cancer Center
11101 New York
United StatesRekrutierend» Google-Maps

Peter MacCallum Cancer Centre; Medical Oncology
3000 Melbourne
AustraliaAktiv, nicht rekrutierend» Google-Maps

Princess Margaret Cancer Center
M5G 1Z5 Toronto
CanadaAktiv, nicht rekrutierend» Google-Maps

Rigshospitalet, Onkologisk Klinik; Klinisk Forskningsenhed
2100 København Ø
DenmarkRekrutierend» Google-Maps

Amsterdam UMC Location VUMC
1081 HV Amsterdam
NetherlandsAbgeschlossen» Google-Maps

Clinica Universitaria de Navarra
31008 Pamplona
SpainAktiv, nicht rekrutierend» Google-Maps

Vall d?Hebron Institute of Oncology (VHIO), Barcelona
08035 Barcelona
SpainAktiv, nicht rekrutierend» Google-Maps

Clinica Universidad de Navarra Madrid; Servicio de Oncología
28027 Madrid
SpainAktiv, nicht rekrutierend» Google-Maps

START Madrid-FJD, Hospital Fundacion Jimenez Diaz
28040 Madrid
SpainAbgeschlossen» Google-Maps

Alle anzeigen

Studien-Informationen

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).

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. 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))

2. Percentage of Participants with Dose Limiting Toxicities (DLTs) (Time Frame - Cycle 1 (each cycle is 21 days))

Secondary outcome:

1. Serum Concentration of RO7428731 (Time Frame - Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months))

2. 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))

3. Objective Response Rate (ORR) (Time Frame - From start of study treatment up to approximately 3 years)

4. Disease Control Rate (DCR) (Time Frame - From start of study treatment up to approximately 3 years)

5. 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))

6. 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))

7. Overall Survival (OS) (Time Frame - From start of study treatment to the time of death from any cause (up to approximately 3 years))

Studien-Arme

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.

Geprüfte Regime

RO7428731:
Participants will receive RO7428731 as described.

Quelle: ClinicalTrials.gov

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