RO7428731 for Glioblastoma

Recruiting at 14 trial locations

Overseen By Reference Study ID Number: BP42573 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hoffmann-La Roche

Must not be taking: Anti-EGFRvIII agents

Disqualifiers: Infratentorial tumors, Metastatic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, RO7428731, for safety and effectiveness in patients with a specific type of brain cancer (glioblastoma) that has a particular mutation. The drug works by targeting and binding to the mutated cancer cells to stop their growth. This mutation is common in glioblastoma and makes the cancer grow faster and resist standard treatments.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have received certain prior treatments for GBM, so it's best to discuss your current medications with the study team.

What makes the drug RO7428731 unique for treating glioblastoma?

The drug RO7428731 is unique for treating glioblastoma because it may target specific vulnerabilities in uncommon glioblastoma subsets, such as high tumor mutational burden or specific gene fusions, which are not effectively addressed by standard treatments like temozolomide or bevacizumab. ^{1 2 3 4 5}

What data supports the effectiveness of the drug RO7428731 for glioblastoma?

The research suggests that combining chemotherapy with radiation, like temozolomide with radiotherapy, improves survival rates in glioblastoma patients, especially those with specific genetic markers. This indicates that targeted therapies, potentially similar to RO7428731, could be effective in treating glioblastoma by improving patient outcomes. ^{3 6 7 8 9}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with a specific brain cancer called EGFRvIII-positive glioblastoma, either newly diagnosed or recurrent. They should have completed standard treatments and be expected to live at least 12 weeks. Participants need good physical function (KPS Score >=70%) and proper organ function. Those with high bleeding risks, more than two GBM recurrences, certain tumor locations, or previous extensive GBM treatments are excluded.

Inclusion Criteria

At least one measurable GBM lesion as per Response Assessment in Neuro-Oncology (RANO) criteria prior to initiation of study treatment.

Willingness to abide by contraceptive measures for the duration of the study.

My tumor's MGMT status is either unmethylated or methylated.

Exclusion Criteria

I do not have any conditions that cause unusual bleeding.

My GBM has recurred more than twice.

My tumor is located in a critical area of the brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Participants with recurrent GBM receive RO7428731, IV in a dosing schedule determined in Part I

Duration not specified

Dose Escalation

Participants with newly diagnosed GBM receive RO7428731, IV, up to one year or until disease progression, withdrawal of consent, unacceptable toxicity, or death

Up to 1 year

Dose Expansion

Participants with newly diagnosed GBM receive RO7428731, IV in maximum of two dose expansion cohorts at a dose(s) not exceeding the MTD established in Part I

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RO7428731

Trial Overview The study tests RO7428731's safety and effectiveness as a solo treatment in those with EGFRvIII-positive glioblastoma. It's an open-label trial meaning everyone knows what treatment they're getting. The drug’s effects on the body (pharmacokinetics), immune response (immunogenicity), how it works against cancer cells (pharmacodynamics), and its initial success in shrinking tumors will be studied.

How Is the Trial Designed?

Group I: Part IV A: Dose-Expansions Cohort Experimental Treatment 1 Intervention

Participants with recurrent GBM will receive RO7428731, IV at specified doses and dosing schedules.

Group II: Part III: Safety Run-in Experimental Treatment 1 Intervention

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.

Group III: Part II: Dose-Expansion(s) Experimental Treatment 1 Intervention

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.

Group IV: Part I: Dose Escalation Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Adding nitrosourea-based chemotherapy to radiotherapy has been shown to increase progression-free survival in patients with grade II and III gliomas, although it does not improve overall survival.

Upcoming phase III trials will investigate whether adding temozolomide to radiotherapy can enhance overall survival in grade II/III gliomas, while also assessing cognitive function and quality of life for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and radiation in low-grade and anaplastic gliomas: temoradiation. Schiff, D.[2018]

Intracerebral administration of ipilimumab (IPI) and nivolumab (NIVO) after maximal safe resection of recurrent glioblastoma (rGB) was found to be feasible and safe, with mild immune-related adverse events and no significant central nervous system toxicity observed.

The treatment resulted in a median overall survival of 38 weeks, which is favorable compared to historical data, suggesting that this approach may improve outcomes for patients with rGB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral administration of CTLA-4 and PD-1 immune checkpoint blocking monoclonal antibodies in patients with recurrent glioblastoma: a phase I clinical trial. Duerinck, J., Schwarze, JK., Awada, G., et al.[2022]

Glioblastomas, particularly the IDH-wildtype type, are challenging to treat, with standard care involving surgery, radiotherapy, and temozolomide chemotherapy since 2005, but no pharmacological treatments have significantly improved overall survival.

Targeting specific genetic vulnerabilities in rare glioblastoma subsets and focusing on the tumor microenvironment may offer new avenues for treatment, highlighting the need for improved clinical trial designs to test these strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular targeted therapy of glioblastoma. Le Rhun, E., Preusser, M., Roth, P., et al.[2019]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Temozolomide and radiation in low-grade and anaplastic gliomas: temoradiation. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Genetic biomarkers of drug response for small-molecule therapeutics targeting the RTK/Ras/PI3K, p53 or Rb pathway in glioblastoma. [2019]

3. France pubmed.ncbi.nlm.nih.gov

[Association of radiotherapy and chemotherapy-targeted therapies in glioblastomas]. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Intracerebral administration of CTLA-4 and PD-1 immune checkpoint blocking monoclonal antibodies in patients with recurrent glioblastoma: a phase I clinical trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

TP53 mutated glioblastoma stem-like cell cultures are sensitive to dual mTORC1/2 inhibition while resistance in TP53 wild type cultures can be overcome by combined inhibition of mTORC1/2 and Bcl-2. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Molecular targeted therapy of glioblastoma. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Genetic driver mutations introduced in identical cell-of-origin in murine glioblastoma reveal distinct immune landscapes but similar response to checkpoint blockade. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Elucidating tumour-associated microglia/macrophage diversity along glioblastoma progression and under ACOD1 deficiency. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Clinically relevant glioblastoma patient-derived xenograft models to guide drug development and identify molecular signatures. [2023]