89Zr-DFO-nimotuzumab for Lung and Colorectal Cancer

Overseen By Rajan Rakheja, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Saskatchewan

Must not be taking: Anti-EGFR antibodies

Disqualifiers: Pregnancy, Nursing, PET intolerance, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 week

14 Participants Needed

Trial Summary

What is the purpose of this trial?

Over-expression of Epidermal Growth Factor Receptor (EGFR) on cells occurs in all aggressive cancers of epithelial origin. Existing tests for monitoring EGFR expression are invasive and not reliable. There needs to be a better way to measure EGFR expression in cancerous tumors to better tailor cancer treatments. This clinical trial aims to demonstrate the feasibility of imaging cancers that express EGFR using 89Zr-DFO-nimotuzumab and Positron Emission Tomography (PET)/Computerized Tomography (CT). By non-invasively imaging the status of EGFR, 89Zr-DFO-nimotuzumab could be used to assist in the identification of patients who are likely to respond to anti-EGFR treatments, including nimotuzumab. The hypothesis is that 89Zr-DFO-nimotuzumab will accumulate to tumors over-expressing EGFR making them visible when imaged with PET/CT. This hypothesis will be tested in this study, along with the optimal imaging time and diagnostic ability.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, it does require that participants have not previously been treated with anti-EGFR antibodies.

What data supports the effectiveness of the drug 89Zr-DFO-nimotuzumab for lung and colorectal cancer?

Research shows that nimotuzumab, a component of 89Zr-DFO-nimotuzumab, targets the epidermal growth factor receptor (EGFR), which is often overactive in cancers like non-small cell lung cancer (NSCLC). Studies have demonstrated that nimotuzumab can improve outcomes when combined with other treatments, and similar drugs targeting EGFR have shown clinical benefits. ^{1 2 3 4 5}

Is 89Zr-DFO-nimotuzumab safe for human use?

Nimotuzumab, which is part of 89Zr-DFO-nimotuzumab, has been tested in various studies and is generally well-tolerated in humans. In a study involving severe COVID-19 patients, nimotuzumab was very well-tolerated with only mild or moderate side effects in a small number of patients. This suggests that nimotuzumab is generally safe for human use. ^{1 3 5 6 7}

How is the drug 89Zr-DFO-nimotuzumab unique for lung and colorectal cancer?

89Zr-DFO-nimotuzumab is unique because it combines nimotuzumab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), with a radioactive component (89Zr) for PET imaging, allowing for both treatment and precise monitoring of EGFR expression in tumors, which is not typically available with standard therapies. ^{1 2 5 8 9}

Eligibility Criteria

This trial is for adults aged 18-80 with EGFR-positive lung or colorectal cancer who haven't been treated with anti-EGFR antibodies. They must be in good health, not pregnant or nursing, able to consent, and have a tumor size of at least 1.5 cm. It's not suitable for those unable to undergo a 60-minute PET scan.

Inclusion Criteria

I have never been treated with anti-EGFR antibodies.

Able to give informed consent.

My cancer has a tumor or spread that is at least 1.5 cm big.

Exclusion Criteria

I cannot stay still for 60 minutes during a PET scan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an i.v. injection of 89Zr-DFO-nimotuzumab and undergo imaging at multiple time points

1 week

4 visits (in-person)

Follow-up

Participants are monitored for any adverse events until day 30 post administration

3 weeks

1 visit (in-person)

Treatment Details

Interventions

• 89Zr-DFO-nimotuzumab

Trial Overview The study tests if the drug 89Zr-DFO-nimotuzumab can help image cancers expressing EGFR using PET/CT scans non-invasively. Participants will receive either a high (50 mg) or low (1 mg) dose of the drug to determine its effectiveness and optimal imaging time.

Participant Groups

Group I: Establish Imaging Time Experimental Treatment 1 Intervention

Participants will receive an i.v. injection of 50 mg 2 mCi 89Zr-DFO-nimotuzumab. Participants will undergo imaging at four different time points till day 7 after infusion. Vitals, blood sample and urine sample will be collected every time before imaging. Participants will be followed up for any adverse event until day 30 post administration

Group II: Establish Cold Dose Experimental Treatment 1 Intervention

Participants will receive an i.v. injection of 1 mg 2 mCi 89Zr-DFO-nimotuzumab. Participants will undergo imaging at four different time points till day 7 after infusion. Vitals, blood sample and urine sample will be collected every time before imaging. Participants will be followed up for any adverse event until day 30 post administration

Group III: Diagnostic Quality Experimental Treatment 1 Intervention

Participants will receive an i.v. injection of 50 mg 2 mCi 89Zr-DFO-nimotuzumab. Participants will undergo imaging once at the best time calculated from arm 1 participants. Vitals, blood sample and urine sample will be collected before imaging. Participants will be followed up for any adverse event until day 30 post administration

Who Is Running the Clinical Trial?

University of Saskatchewan

Lead Sponsor

Trials

261

Recruited

156,000+

Findings from Research

89Zr-matuzumab was developed as a PET imaging probe to monitor treatment responses in colorectal cancer, showing high uptake in EGFR-positive tumors and confirming its binding to noncompeting epitopes of EGFR.

The nimotuzumab-PEG6-DM1 antibody-drug conjugate demonstrated significantly improved efficacy in targeting colorectal cancer cells, achieving complete tumor remission in 2 out of 3 mice treated, indicating its potential as an effective therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous Imaging and Therapy Using Epitope-Specific Anti-Epidermal Growth Factor Receptor (EGFR) Antibody Conjugates. Tikum, AF., Nambisan, AK., Ketchemen, JP., et al.[2022]

Current treatments for non-small cell lung cancer (NSCLC) have a low 5-year survival rate of only 15%, highlighting the need for improved therapies targeting specific tumor pathways.

Nimotuzumab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has shown clinical benefits in NSCLC and may be expanded for use in additional treatment settings due to its effectiveness against the upregulated EGFR found in 40%-80% of NSCLC cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of nimotuzumab in the treatment of non-small cell lung cancer. Boland, W., Bebb, G.[2021]

In a study of 59 patients with advanced nonsmall cell lung cancer, the combination of nimotuzumab with chemotherapy (docetaxel and carboplatin) significantly prolonged progression-free survival by 1 month compared to chemotherapy alone.

Nimotuzumab was well tolerated, with only mild skin rashes reported, indicating a favorable safety profile while potentially enhancing the effectiveness of treatment as shown by significant decreases in certain tumor markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial on docetaxel and carboplatin therapy with or without nimotuzumab for the treatment of advanced nonsmall cell lung cancer. Qi, D., Cui, Y., Wang, Q., et al.[2018]

In a phase 2 trial involving 40 patients with unresectable locally advanced non-small-cell lung cancer, the addition of nimotuzumab to chemoradiotherapy was well tolerated, achieving a high treatment completion rate of 87.2% without severe adverse effects.

The treatment showed promising efficacy, with an objective response rate of 69.2% and a 5-year overall survival rate of 58.4%, particularly benefiting patients with squamous cell carcinoma, who had a 5-year progression-free survival rate of 50.0%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer. Yamamoto, N., Harada, H., Okamoto, I., et al.[2021]

89Zr-DFO-nimotuzumab, a PET probe targeting EGFR, demonstrated high tumor uptake in mice with EGFR-positive tumors, indicating its potential effectiveness for imaging in cancer diagnostics.

The study showed that 89Zr-DFO-nimotuzumab has a low projected human effective dose and no significant normal tissue toxicity, suggesting it is safe for potential use in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-nimotuzumab for immunoPET imaging of epidermal growth factor receptor I. Chekol, R., Solomon, VR., Alizadeh, E., et al.[2022]

In a study involving 1,151 severe or critical COVID-19 patients treated with nimotuzumab, the recovery rate was significantly higher at 72% compared to 42% in a matched control group, indicating its potential efficacy in improving patient outcomes.

Nimotuzumab was well-tolerated with only mild to moderate adverse events reported in 19 patients, suggesting it is a safe treatment option for severe COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nimotuzumab Increases the Recovery Rate of Severe and Critical COVID-19 Patients: Evaluation in the Real-World Scenario. Diaz, H., Jiménez, J., Hernández, A., et al.[2022]

Nimotuzumab, a monoclonal antibody targeting the epidermal growth factor receptor, was found to be safe for patients with inoperable esophageal tumors, with only 1.3% experiencing serious adverse events, mostly mild to moderate in severity.

Patients treated with nimotuzumab alongside chemotherapy and radiotherapy achieved a median overall survival of 12.2 months and a median progression-free survival of 7.8 months, indicating improved survival outcomes and quality of life compared to those not receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nimotuzumab in the Treatment of Inoperable Esophageal Tumors of Epithelial Origin. González Fernández, S., Amador García, Y., Boris Porras, LG., et al.[2022]

In a study of 13 patients with advanced lung squamous cell carcinoma, nimotuzumab combined with chemotherapy showed an overall response rate of 23.1%, with a higher response rate of 33.3% in patients who were EGFR positive.

The treatment was generally well-tolerated, with only mild non-hematological toxicities and moderate hematological toxicities observed in 23.1% of patients, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nimotuzumab Combined with Chemotherapy as Second- or Later-line in the Treatment of Advanced Lung Squamous Cell Carcinoma]. Luo, Y., Li, J., Wang, Y., et al.[2018]

The use of 89ZrCl4 for radiolabeling monoclonal antibodies like trastuzumab and cetuximab resulted in high specific activity and maintained over 95% purity for at least 3 days when formulated with L-methionine, indicating effective preparation for immuno-PET imaging.

89Zr-DFO-trastuzumab demonstrated sustained reactivity toward its target antigen in PET/CT imaging of lung cancer models, suggesting its potential utility in precision medicine for cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-Chloride Can Be Used for Immuno-PET Radiochemistry Without Loss of Antigen Reactivity In Vivo. Pandya, DN., Bhatt, NB., Almaguel, F., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Simultaneous Imaging and Therapy Using Epitope-Specific Anti-Epidermal Growth Factor Receptor (EGFR) Antibody Conjugates. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

The emerging role of nimotuzumab in the treatment of non-small cell lung cancer. [2021]

3. India pubmed.ncbi.nlm.nih.gov

A clinical trial on docetaxel and carboplatin therapy with or without nimotuzumab for the treatment of advanced nonsmall cell lung cancer. [2018]

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

Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer. [2021]

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

89Zr-nimotuzumab for immunoPET imaging of epidermal growth factor receptor I. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Nimotuzumab Increases the Recovery Rate of Severe and Critical COVID-19 Patients: Evaluation in the Real-World Scenario. [2022]

7. Egypt pubmed.ncbi.nlm.nih.gov

Nimotuzumab in the Treatment of Inoperable Esophageal Tumors of Epithelial Origin. [2022]

8. China pubmed.ncbi.nlm.nih.gov

[Nimotuzumab Combined with Chemotherapy as Second- or Later-line in the Treatment of Advanced Lung Squamous Cell Carcinoma]. [2018]

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

89Zr-Chloride Can Be Used for Immuno-PET Radiochemistry Without Loss of Antigen Reactivity In Vivo. [2020]