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Closed (no longer recruiting)Last updated: 26 February 2024

This phase I study is evaluating how safe and effective a new cancer drug (RO7428731) is in people with newly diagnosed or recurrent glioblastomaAn 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

Clinical summary

Summary

This trial is assessing RO7428731 administered as a monotherapy in participants with newly diagnosed or recurrent epidermal growth factor receptor variant III (EGFRvIII)-positive glioblastoma (GBM). The trial has four parts. In 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. In Part II (Dose Expansion), participants with newly diagnosed GBM will receive RO7428731, via IV, in maximum of two dose expansion cohorts at a dose(s) not exceeding the maximum tolerated dose (MTD) established in Part I. In 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. In Part IV (Dose-Expansions Cohort), participants with recurrent GBM will receive RO7428731, IV at specified doses and dosing schedules.

Conditions

This trial is treating patients with epidermal growth factor receptor variant III (EGFRvIII)-positive glioblastoma

Cancer

Brain and Spinal Cancers Brain and Spinal

Age

People18+

Phase

I

More information

Trial Identifiers

Use the hyperlinks, where available to access additional clinical trial information.

Trial sponsor

Hoffmann-La Roche

Scientific 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

Eligibility

Inclusion

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

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.

Inclusion

  • You have been diagnosed with cancer, but have not received any treatment.
  • You have had treatment, but your cancer has come back.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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