A Study to Evaluate the Safety, Tolerability and Immunogenicity of EGFR(V)-EDV-Dox in Subjects With Recurrent GBM

(CerebralEDV Trial)

Recruiting at 1 trial location

Overseen By Kelly Szajna, RN BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Engeneic Pty Limited

Must not be taking: Anti-angiogenics, Anticoagulants

Disqualifiers: CNS bleeding, Coronary artery disease, HIV, others

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

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

9 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain treatments like radiation, specific chemotherapies, and anticoagulation therapy must not have been received recently. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug EGFR(V)-EDV-Dox?

Research shows that targeting the epidermal growth factor receptor (EGFR) can be effective in treating certain cancers, as seen in studies where combining EGFR inhibitors with other treatments improved outcomes in non-small cell lung cancer. This suggests that EGFR-targeted therapies, like EGFR(V)-EDV-Dox, may have potential benefits in cancer treatment. ^{1 2 3 4 5}

Is EGFR(V)-EDV-Dox safe for humans?

EGFR inhibitors, like EGFR-TKIs, have been used in treating certain cancers and are generally considered tolerable, but they can cause side effects such as diarrhea, liver issues, skin problems, and lung disease. Serious reactions are rare, but it's important for doctors to manage these side effects properly. ^{6 7 8 9 10}

How does the drug EGFR(V)-EDV-Dox differ from other treatments for cancer?

EGFR(V)-EDV-Dox is unique because it targets the EGF receptor (a protein on cell surfaces involved in cell growth) which is often overactive in cancers, potentially making it effective against tumors that rely on this pathway. This drug may offer a novel approach by specifically addressing the mechanisms that contribute to cancer cell invasiveness and progression, unlike standard treatments that may not target these specific pathways. ^{11 12 13 14 15}

What is the purpose of this trial?

This trial tests a new drug that combines targeted therapy with chemotherapy for patients with recurring brain cancer. The drug aims to target cancer cells specifically, delivering chemotherapy directly to them.

Research Team

Stuart A Grossman, M.D.

Principal Investigator

Johns Hopkins University

Himanshu Brahmbhatt, Ph. D

Principal Investigator

Engeneic Pty Limited

Gary L Gallia, M.D., Ph.D

Principal Investigator

Johns Hopkins University

Jennifer MacDiarmid, Ph.D

Principal Investigator

Engeneic Pty Limited

Eligibility Criteria

Inclusion Criteria

Karnofsky Performance Status (KPS) ≥ 60%.

Life expectancy ≥ 3 months.

Pathologically documented, and definitively diagnosed recurrent World Health Organization (WHO) Grade IV astrocytoma (GBM).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EGFR(V)-EDV-Dox weekly for 7 weeks via IV infusion, followed by radiological evaluation at week 8

8 weeks

8 visits (in-person)

Safety Follow-up

A safety follow-up visit is performed 30 (+5) days after the last dose of drug

5 weeks

1 visit (in-person)

Long-term Follow-up

Participants are monitored approximately every 1 month for 12 months, then every 2-3 months for survival

12 months

Treatment Details

Interventions

• EGFR(V)-EDV-Dox

Participant Groups

Group I: EGFR(V)-EDV-Dox Experimental Treatment 1 Intervention

EGFR(V)-EDV-Dox administered via 20 minute intravenous infusion once a week for seven weeks (1 Cycle). Subjects will receive one of two dose levels: 5 x 10\^9 or 8 x 10\^9. All subjects will undergo an adapted dose escalation regime in the first cycle of treatment. For subsequent cycles all doses will be administered at full strength (5x10\^9 or 8x10\^9 EGFR(V)-EDV-Dox). Subjects may receive further cycles of treatment if the tumor remains stable or is responding, and/or they are deriving clinical benefit from the therapy and are tolerating treatment.

Who Is Running the Clinical Trial?

Engeneic Pty Limited

Lead Sponsor

Trials

2

Recruited

30+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Findings from Research

In the Phase III RELAY trial, the combination of ramucirumab and erlotinib (RAM + ERL) significantly improved progression-free survival (PFS) in European and US patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), with a median PFS of 20.6 months compared to 10.9 months for the placebo group.

The safety profile of RAM + ERL was consistent with the overall population, with hypertension being the most common severe side effect, indicating that ramucirumab is a safe and effective addition to standard EGFR-TKI therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated, EGFR-mutated, metastatic non-small cell lung cancer: Europe/United States subset analysis. Ponce Aix, S., Novello, S., Garon, EB., et al.[2023]

EGFR inhibitors significantly improve objective response rates (ORR), disease control rates (DCR), and progression-free survival (PFS) in advanced non-small cell lung cancer patients with EGFR mutations compared to non-targeted chemotherapy, based on a review of 21 studies involving 4,250 patients.

Despite the improved response and control rates with EGFR inhibitors, overall survival (OS) did not show significant differences compared to non-targeted chemotherapy or older EGFR inhibitors, indicating that better short-term outcomes do not necessarily translate to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of EGFR Inhibitors in the Treatment of EGFRPositive NSCLC Patients: A Meta-Analysis. Dang, A., Dang, S., Vallish, BN.[2021]

Targeting the epidermal growth factor receptor (EGFR) is a promising strategy in cancer therapy, as it plays a crucial role in processes like cancer cell growth and metastasis, with several anti-EGFR drugs currently in advanced clinical development.

Cetuximab and gefitinib are two key anti-EGFR drugs that have shown efficacy in treating specific types of cancer, such as advanced colorectal cancer and chemoresistant non-small cell lung cancer, respectively, highlighting their potential in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidermal growth factor receptor inhibitors in cancer treatment. Ciardiello, F.[2018]

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) significantly enhance progression-free and overall survival in patients with non-small cell lung cancer (NSCLC) who have activating mutations in the EGFR gene.

Despite their efficacy, EGFR-TKIs can cause several adverse events, such as diarrhea, liver toxicity, and skin issues, which can negatively impact patients' quality of life and adherence to treatment; therefore, managing these side effects is crucial for effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of EGFR-TKIs for EGFR mutation-positive non-small cell lung cancer. Zhou, JY., Liu, SY., Wu, YL.[2021]

References

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

Epidermal growth factor receptor (EGFr); results of a 6 year follow-up study in operable breast cancer with emphasis on the node negative subgroup. [2019]

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

RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated, EGFR-mutated, metastatic non-small cell lung cancer: Europe/United States subset analysis. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Erlotinib for Patients with EGFR Wild-Type Metastatic NSCLC: a Retrospective Biomarkers Analysis. [2020]

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Altered Regulation of HIF-1α in Naive- and Drug-Resistant EGFR-Mutant NSCLC: Implications for a Vascular Endothelial Growth Factor-Dependent Phenotype. [2022]

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Efficacy and Toxicity of Combined Inhibition of EGFR and VEGF in Patients With Advanced Non-small Cell Lung Cancer Harboring Activating EGFR Mutations: A Systematic Review and Meta-analysis. [2023]

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Efficacy and Safety of EGFR Inhibitors in the Treatment of EGFRPositive NSCLC Patients: A Meta-Analysis. [2021]

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Epidermal growth factor receptor inhibitors in cancer treatment. [2018]

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The survival after discontinuation of EGFR-TKIs due to intolerable adverse events in patients with EGFR-mutated non-small cell lung cancer. [2023]

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Therapy-related myeloid leukemia during erlotinib treatment in a non-small cell lung cancer patient: A case report. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Safety of EGFR-TKIs for EGFR mutation-positive non-small cell lung cancer. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

EGF receptor in neoplasia and metastasis. [2019]

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

A novel EGFR isoform confers increased invasiveness to cancer cells. [2018]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Mechanisms of EGF receptor regulation in breast cancer cells. [2019]

14. England pubmed.ncbi.nlm.nih.gov

Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling network. [2018]

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

The epidermal growth factor receptor is not a receptor for vaccinia virus. [2020]