EGFR Inhibitor for Brain Cancer

Recruiting at 2 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must be taking: EGFR TKIs

Must not be taking: Anticonvulsants, CYP3A inducers

Disqualifiers: Pregnancy, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 3

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the optimal dose and assess the side effects of a new treatment, WSD0922-FU, for brain and lung cancers that have spread to the central nervous system. WSD0922-FU, an EGFR inhibitor, blocks the EGFR protein, often involved in cancer growth. The trial includes different groups to evaluate the treatment's effectiveness for individuals with glioblastoma, anaplastic astrocytoma, or non-small cell lung cancer affecting the brain or spinal cord. Those who have previously had these cancers and experienced a recurrence or worsening may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to receive it.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that WSD0922-FU undergoes careful safety testing. This new treatment aims to block a protein called EGFR, which aids the growth of some cancers. Early studies suggest that WSD0922-FU can reach brain tumors, offering hope for treating brain and spinal cord cancers.

This trial marks the first time WSD0922-FU is tested in humans. The main goal is to determine the best dose and monitor any side effects. As an early phase trial, detailed safety information is not yet available. However, this phase is crucial for understanding how well people tolerate WSD0922-FU and identifying potential side effects.

New treatments like WSD0922-FU are generally closely monitored in these trials to ensure patient safety and allow for necessary adjustments. If successful, this trial could lead to further studies and, eventually, wider use if proven safe and effective. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about WSD0922-FU for brain cancer because it targets the EGFR (epidermal growth factor receptor), which plays a key role in tumor growth and progression. Unlike current treatments like chemotherapy and radiation, this drug is designed to specifically inhibit EGFR, potentially offering a more targeted approach with fewer side effects. Additionally, the oral administration of WSD0922-FU provides a more convenient option compared to some existing treatments that require hospital visits or intravenous delivery. This new mechanism and delivery method might lead to improved outcomes for patients with brain tumors such as glioblastoma multiforme (GBM) and brain metastases from non-small cell lung cancer (NSCLC).

What evidence suggests that WSD0922-FU could be an effective treatment for brain cancer?

Research has shown that WSD0922-FU effectively targets a protein called EGFR, which is often overly active in many cancers. Studies have found that this treatment can cross the blood-brain barrier, a protective layer around the brain. This capability makes it promising for treating brain tumors like glioblastoma and cancers that have spread to the brain and spinal cord. In mouse studies of glioblastoma, WSD0922-FU improved survival rates. Compared to other treatments targeting EGFR, WSD0922-FU's ability to reach the brain suggests it could offer more benefits for brain cancer patients. In this trial, participants will receive WSD0922-FU in different treatment arms, including dose escalation and dose expansion cohorts, to further evaluate its effectiveness and safety. These promising results make it an exciting option for ongoing research. ^{1 3 4 6 7}

Who Is on the Research Team?

Sani Kizilbash, MD, MPH

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• WSD0922-FU

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.

How Is the Trial Designed?

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+

Wayshine Biopharm, Inc.

Industry Sponsor

Trials

3

Recruited

200+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

Published Research Related to This Trial

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]

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 EGFR type III variant (EGFRvIII) is a tumor-specific target found in various cancers, including glioblastoma, making it a promising candidate for targeted cancer therapies.

Monoclonal antibodies designed to target EGFRvIII can be internalized by cancer cells and can be used alone or with cytotoxic agents, showing potential for effective treatment of tumors expressing this variant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EGFRvIII as a promising target for antibody-based brain tumor therapy. Kuan, CT., Wikstrand, CJ., Bigner, DD.[2019]

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]

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]

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]

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]

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]

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]

The epidermal growth factor receptor (EGFR) is a key target in cancer therapy, particularly in glioblastoma multiforme (GBM), where it is overexpressed in 40-50% of cases, contributing to the aggressive nature of the disease.

Current clinical trials are exploring the efficacy of anti-EGFR monoclonal antibodies and tyrosine kinase inhibitors, with ongoing research into combination therapies and novel approaches like RNA targeting to improve treatment outcomes for patients with GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The epidermal growth factor receptor as a therapeutic target in glioblastoma multiforme and other malignant neoplasms. Loew, S., Schmidt, U., Unterberg, A., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04197934

Study Details | NCT04197934 | WSD0922-FU for the ... This phase I trial studies the side effects and best dose of WSD0922-FU for the treatment of glioblastoma, anaplastic astrocytoma, or non-small cell lung ...

2. mayo.edu mayo.edu/research/clinical-trials/cls-20473609

Clinical Trials The purpose of this study is to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of WSD0922-FU in subjects with recurrent ...

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/egfr-egfrviii-inhibitor-wsd0922-fu?pn=1

Clinical Trials Using EGFR/EGFRvIII Inhibitor WSD0922-FU WSD0922-FU for the treatment of glioblastoma, anaplastic astrocytoma, or non-small cell lung cancer with central nervous system metastases.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10263119/

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

5. mycancergenome.org mycancergenome.org/content/drugs/wsd0922-fu/

wsd0922-fu Compared to other EGFR inhibitors that are not able to penetrate the BBB, WSD0922-FU may have therapeutic benefits in brain tumors, such as glioblastoma (GBM) ...

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/222100

WSD0922-FU for the Treatment of Glioblastoma, Anaplastic ... This phase I trial studies the side effects and best dose of WSD0922-FU for the treatment of glioblastoma, anaplastic astrocytoma, or non-small cell lung ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06868485

A Study to Assess the Efficacy of WSD0922-FU in Patients ... The clinical development program with WSD0922-FU will assess the safety and efficacy of WSD0922-FU in patients with advanced NSCLC whose cancers have progressed ...