What is the mechanism of action of this treatment?

Glioblastoma treatments often target the Epidermal Growth Factor Receptor variant III (EGFRvIII), a mutation commonly found in these tumors. EGFRvIII inhibitors, like RO7428731, work by blocking the signaling pathways that promote tumor growth and survival, which is crucial for slowing disease progression. Additionally, standard treatments include temozolomide, an oral chemotherapy that damages the DNA of cancer cells, and radiation therapy, which uses high-energy rays to kill or damage cancer cells. These treatments aim to control tumor growth, alleviate symptoms, and extend survival, addressing the aggressive nature of Glioblastoma.

What side effects are associated with this type of intervention?

Common treatments for Glioblastoma, particularly those involving EGFRvIII inhibition like RO7428731, often have side effects including infusion-related reactions, skin rashes, fatigue, gastrointestinal issues (such as nausea and diarrhea), and hematologic toxicities like neutropenia. Antibody-drug conjugates (ADCs) used in these treatments can also cause hair loss due to the bystander effect of the cytotoxic agents.

What prior FDA approvals exist?

The FDA has approved several treatments for Glioblastoma, including temozolomide, an oral chemotherapy drug, and bevacizumab, an angiogenesis inhibitor. These treatments aim to slow tumor growth and manage symptoms. While specific FDA approvals for EGFRvIII inhibitors in Glioblastoma are not detailed, ongoing research, such as the trial of RO7428731, is exploring targeted therapies that inhibit the EGFRvIII mutation, which is a promising area for future treatment options.

What other types of research exist?

Promising novel alternatives to RO7428731 for Glioblastoma patients include: 1) CAR T-cell therapy targeting EGFRvIII, which has shown potential in early-phase trials. 2) Oncolytic virus therapy, such as DNX-2401, which is designed to selectively infect and kill tumor cells. 3) Combination therapies involving immune checkpoint inhibitors (e.g., pembrolizumab) with other agents like bevacizumab. 4) Tumor Treating Fields (TTF) therapy, which uses electric fields to disrupt cancer cell division. These alternatives are being actively researched and may offer new hope for glioblastoma patients.

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Monoclonal Antibodies

RO7428731 for Glioblastoma

Phase 1

Recruiting

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Documented first or second recurrence of GBM

Must not have

Active bleeding or pathological condition that carries a high risk of bleeding, including inherited and acquired coagulopathies

More than two recurrences of GBM

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects of RO7428731 aren't listed here, similar drugs often cause immune reactions, infusion-related discomforts, fatigue, changes in blood counts affecting immunity/clotting/oxygen transport, liver/kidney function alterations and potential allergic responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My brain cancer has come back for the first or second time.

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I have a specific type of brain tumor (EGFRvIII-positive GBM) and have finished standard treatment.

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I have been diagnosed with GBM according to the latest WHO standards.

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I am able to care for myself but may not be able to do active work.

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My cancer tests positive for EGFRvIII.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any conditions that cause unusual bleeding.

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My GBM has recurred more than twice.

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

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My cancer has spread outside of my brain.

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My brain tumor has come back after treatment.

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I have only had surgery, radiation, and temozolomide for my GBM.

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I have not received treatments targeting EGFRvIII, anti-angiogenic therapy, or gene therapy for GBM or gliomas.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Part IV A: Dose-Expansions CohortExperimental Treatment1 Intervention

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

Group II: Part III: Safety Run-inExperimental Treatment1 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 Treatment1 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 EscalationExperimental Treatment1 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.

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Glioblastoma treatments often target the Epidermal Growth Factor Receptor variant III (EGFRvIII), a mutation commonly found in these tumors. EGFRvIII inhibitors, like RO7428731, work by blocking the signaling pathways that promote tumor growth and survival, which is crucial for slowing disease progression. Additionally, standard treatments include temozolomide, an oral chemotherapy that damages the DNA of cancer cells, and radiation therapy, which uses high-energy rays to kill or damage cancer cells. These treatments aim to control tumor growth, alleviate symptoms, and extend survival, addressing the aggressive nature of Glioblastoma.