EGFR Inhibitor for Brain Cancer

Recruiting at2 trial locations

Overseen by Sani Kizilbash, MD, MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Mayo Clinic

Must be taking: EGFR TKIs

Must not be taking: Anticonvulsants, CYP3A inducers

Disqualifiers: Pregnancy, HIV, Hepatitis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called WSD0922-FU for patients with aggressive brain and spinal cord cancers. The drug works by blocking a protein that helps cancer cells grow. The goal is to find the best dose and see if it can effectively treat these hard-to-treat cancers.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications before joining. Specifically, if you are taking enzyme-inducing anticonvulsants or strong inducers and inhibitors of CYP3A, you must stop them at least 14 days before joining. Additionally, if you are taking an EGFR TKI for NSCLC, it must be discontinued prior to registration, with a specific washout period required.

What data supports the effectiveness of the drug WSD0922-FU for brain cancer?

Research shows that targeting the EGFRvIII variant, which is common in brain tumors like glioblastoma, can be effective because this variant is active in promoting tumor growth. WSD-0922, a similar EGFR inhibitor, has shown promise in preclinical studies by improving survival in mouse models of glioblastoma. ^{1 2 3 4 5}

Is the EGFR inhibitor WSD0922-FU safe for humans?

The safety of WSD0922-FU specifically is not detailed in the provided research, but a related EGFR-targeted vaccine for glioblastoma was found to be safe, with no serious adverse events and only mild side effects in patients. ^{1 4 6 7 8}

What makes the drug WSD0922-FU unique for treating brain cancer?

WSD0922-FU is unique because it is a novel inhibitor that can penetrate the brain and specifically targets the EGFR and its mutant form EGFRvIII, which are common drivers in glioblastoma, a type of brain cancer. This drug is designed to overcome the challenges of targeting these proteins, which have been difficult to treat effectively with existing therapies. ^{1 3 4 9 10}

Research Team

Sani Kizilbash, MD, MPH

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for adults with certain brain cancers (glioblastoma, anaplastic astrocytoma) or lung cancer that has spread to the brain. They must have specific genetic changes in their tumors and be in good physical condition. People can't join if they've had certain heart issues, uncontrolled illnesses, severe lung disease, or are unable to stop medications that affect heart rhythm.

Inclusion Criteria

My cancer's EGFR status matches the specific requirements for the study group.

My cancer has an EGFR mutation.

I've had cancer treatment before, my cancer has grown, I can see my cancer on scans, and I'm mostly active.

Exclusion Criteria

I meet specific health and treatment criteria for a study phase.

I do not have any severe illnesses or psychiatric conditions that are not under control.

I have a heart condition that affects my heart's electrical activity.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation

Patients receive WSD0922-FU orally once or twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Regular visits for CT, MRI, and blood sample collection

Dose Expansion

Patients are assigned to one of three cohorts and receive WSD0922-FU with specific protocols for each cohort. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Regular visits for MRI, CT, and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs at 4-6 weeks, then every 2 months until progressive disease, and every 3 months thereafter for up to 5 years.

Up to 5 years

Follow-up visits every 2-3 months

Treatment Details

Interventions

• WSD0922-FU (EGFR/EGFRvIII Inhibitor)

Trial Overview The study tests WSD0922-FU's safety and optimal dose for treating specific brain and lung cancers. It involves collecting tissue samples, imaging tests like CT and MRI scans, possibly surgery, and administering WSD0922-FU which blocks a protein involved in tumor growth.

Participant Groups

Group I: Dose expansion Cohort III (WSD0922-FU) Experimental Treatment 5 Interventions

Patients with NSCLC receive WSD0922-FU PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI and CT during screening and on study, as well as blood sample collection on study. Patients with LM also undergo collection of CSF samples on study. Patients may also undergo optional blood sample collection on study.

Group II: Dose expansion Cohort II (WSD0922-FU, surgery) Experimental Treatment 5 Interventions

Patients with BTP receive a single dose of WSD0922-FU prior to surgery. Patients then undergo surgical resection of brain tumor. After surgery, patients receive WSD0922-FU PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI during screening and on study, as well as blood sample collection on study.

Group III: Dose expansion Cohort I (WSD0922-FU) Experimental Treatment 4 Interventions

Patients with GBM/AA receive WSD0922-FU PO on days 1 and 4 of cycle 0. Patients then receive WSD0922-FU PO BID on days 1-28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI during screening and on study, as well as blood sample collection on study. Patients may undergo additional optional blood sample collection on study.

Group IV: Dose escalation (WSD0922-FU) Experimental Treatment 5 Interventions

Patients receive WSD0922-FU PO QD or BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and blood sample collection on study. Patients with NSCLC with LM also undergo collection of CSF samples on study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

Wayshine Biopharm, Inc.

Industry Sponsor

Trials

3

Recruited

200+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

Dr. Patrizia Cavazzoni

Food and Drug Administration (FDA)

Chief Medical Officer

MD from Harvard Medical School

Dr. Martin A. Makary

Food and Drug Administration (FDA)

Chief Executive Officer

MD from Sidney Kimmel Medical College, MPH from Harvard T.H. Chan School of Public Health

Findings from Research

EGFRvIII, a common variant in glioblastoma multiforme (GBM), is constitutively active due to a deletion in its structure, which enhances tumor growth and resistance to therapy, making it a key target for treatment.

Targeting EGFRvIII is promising for GBM therapy because it is not expressed in normal tissues, allowing for more precise treatment options that could minimize damage to healthy cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The EGFRvIII variant in glioblastoma multiforme. Gan, HK., Kaye, AH., Luwor, RB.[2022]

WSD-0922, a novel EGFR inhibitor, demonstrated comparable efficacy to erlotinib in inhibiting EGFR signaling in both in vitro and in vivo models, but showed a significant survival advantage in a glioblastoma patient-derived xenograft model.

WSD-0922 exhibited better central nervous system (CNS) penetration than erlotinib, leading to effective tumor growth suppression and improved survival rates in treated mice, suggesting its potential as a more effective treatment for glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WSD-0922, a novel brain-penetrant inhibitor of epidermal growth factor receptor, promotes survival in glioblastoma mouse models. Conage-Pough, JE., Stopka, SA., Oh, JH., et al.[2023]

EGFR inhibitors, like gefitinib, have been approved for treating advanced non-small-cell lung cancer (NSCLC) based on a phase 2 study showing a 10% response rate in patients with refractory disease, indicating some efficacy in a specific patient group.

Despite the approval, larger randomized trials showed no survival benefit when gefitinib was added to chemotherapy for untreated patients, highlighting the need for further research to identify which patients are most likely to benefit from EGFR-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting epidermal growth factor receptor--are we missing the mark? Dancey, JE., Freidlin, B.[2018]

Epidermal growth factor receptor (EGFR) inhibitors, including monoclonal antibodies like cetuximab and tyrosine kinase inhibitors like gefitinib, have been approved for cancer treatment, highlighting their efficacy as targeted therapies in epithelial cancers.

Understanding the biology of EGFR interactions can lead to more selective cancer treatments with reduced side effects, although further research is needed to optimize combinations with other therapies and identify the best patient candidates for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology of interactions: antiepidermal growth factor receptor agents. Harari, PM., Allen, GW., Bonner, JA.[2022]

The dendritic cell-based vaccine targeting the EGFRvIII mutation in glioblastoma multiforme (GBM) was found to be safe, with no serious adverse events and only mild grade 2 toxicities reported among patients.

Patients showed a significant immune response to the vaccine, with a median survival time of 18.7 months post-vaccination, indicating that targeting the EGFRvIII mutation could be an effective immunotherapy approach for GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. Sampson, JH., Archer, GE., Mitchell, DA., et al.[2022]

Cediranib, a potent receptor tyrosine kinase inhibitor, did not enhance the effectiveness of radiation therapy in glioblastoma models but significantly improved the effectiveness of temozolomide (TMZ) treatment.

The study involved U87 glioblastoma xenografts expressing either the wild-type EGFR or the mutant EGFRvIII, and the combination of cediranib with TMZ suggests a promising new treatment strategy for better tumor control in glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cediranib enhances control of wild type EGFR and EGFRvIII-expressing gliomas through potentiating temozolomide, but not through radiosensitization: implications for the clinic. Wachsberger, PR., Lawrence, RY., Liu, Y., et al.[2021]

EGFRvIII, a mutant form of the epidermal growth factor receptor, is a key driver of glioblastoma (GBM) and relies on PDGFRA signaling for tumor growth, highlighting a potential therapeutic target.

In patient-derived xenograft models, effective anti-tumor treatment requires simultaneous inhibition of both EGFRvIII and PDGFRA, suggesting that targeting these pathways together could improve treatment outcomes for GBM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EGFRvIII tumorigenicity requires PDGFRA co-signaling and reveals therapeutic vulnerabilities in glioblastoma. Yeo, AT., Jun, HJ., Appleman, VA., et al.[2023]

Cinobufagin, derived from Traditional Chinese Medicine, effectively inhibits the growth of glioblastoma multiforme (GBM) cells with EGFR amplification and PTEN deficiency, enhancing its anti-proliferative effects.

In animal models, cinobufagin not only blocked EGFR signaling and induced apoptosis in cancer cells but also significantly suppressed tumor growth and increased survival rates, suggesting its potential as a therapeutic agent for EGFR-driven tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion. He, K., Wang, GX., Zhao, LN., et al.[2021]

References

1. Scotland pubmed.ncbi.nlm.nih.gov

The EGFRvIII variant in glioblastoma multiforme. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

EGFRvIII as a promising target for antibody-based brain tumor therapy. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The epidermal growth factor receptor as a therapeutic target in glioblastoma multiforme and other malignant neoplasms. [2019]

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

WSD-0922, a novel brain-penetrant inhibitor of epidermal growth factor receptor, promotes survival in glioblastoma mouse models. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Targeting epidermal growth factor receptor--are we missing the mark? [2018]

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

Biology of interactions: antiepidermal growth factor receptor agents. [2022]

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

An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. [2022]

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

Cediranib enhances control of wild type EGFR and EGFRvIII-expressing gliomas through potentiating temozolomide, but not through radiosensitization: implications for the clinic. [2021]

9. England pubmed.ncbi.nlm.nih.gov

EGFRvIII tumorigenicity requires PDGFRA co-signaling and reveals therapeutic vulnerabilities in glioblastoma. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion. [2021]