IRDye800CW-nimotuzumab Imaging for Lung Cancer Surgery

Overseen By Ron Geyer, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Saskatchewan

Must not be taking: Anti-EGFR, Antiarrhythmics

Disqualifiers: Pregnancy, Allergies, Heart disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1-7 days

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method to help surgeons see lung cancer tumors more clearly during surgery. The treatment, IRDye800CW-nimotuzumab, is administered through an IV before surgery and is designed to illuminate cancer cells with excess EGFR protein. The trial examines different doses and timing to determine the safest and most effective use of this imaging method. Individuals with stage I or II non-small cell lung cancer, who haven't had other cancers or treatments, might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have received anti-EGFR antibody therapy within 60 days or are taking certain heart rhythm medications. It's best to discuss your specific medications with the trial team.

What prior data suggests that IRDye800CW-nimotuzumab is safe for use in image-guided lung cancer surgery?

Research has shown that IRDye800CW-nimotuzumab is generally safe based on early lab studies. These studies indicate that combining nimotuzumab with IRDye800CW targets cancer cells without causing the usual side effects associated with targeting EGFR, a protein on cancer cells. This suggests it is likely to be well-tolerated.

In human studies, researchers are determining the safest dose and optimal timing for use during surgery. Although specific safety details for humans aren't provided, the treatment's presence in advanced clinical trials suggests earlier tests did not reveal major safety issues. Participants in these studies receive close monitoring for any side effects, allowing for quick intervention if problems arise. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about IRDye800CW-nimotuzumab for lung cancer surgery because it introduces a novel approach to tumor visualization. Unlike traditional treatments that primarily focus on shrinking tumors, this treatment uses a fluorescent dye linked to nimotuzumab, an antibody that specifically targets cancer cells. This allows surgeons to visualize and remove cancerous tissue more accurately during surgery. By improving surgical precision, it has the potential to enhance outcomes and reduce the likelihood of cancer recurrence.

What evidence suggests that IRDye800CW-nimotuzumab is effective for image-guided lung cancer surgery?

Research has shown that IRDye800CW-nimotuzumab targets lung cancer cells with high levels of a protein called EGFR, often abundant in cancer cells. This targeting enhances tumor visibility, aiding surgeons in identifying cancer during operations. Laboratory studies have demonstrated that this treatment is safe and lacks the harmful effects typically associated with drugs targeting EGFR. Another study found nimotuzumab promising for near-infrared (NIR) imaging, which helps doctors see and remove tumors more precisely. This trial will evaluate different dosing and timing strategies of IRDye800CW-nimotuzumab to determine the optimal approach for improving surgical outcomes by making tumors easier to find and remove. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with Stage I or II non-small cell lung cancer that can be surgically removed. Participants must have good blood counts, no history of other cancers, not received certain anti-cancer drugs recently, and should not be pregnant or nursing. They need to be healthy enough for surgery and without serious heart conditions or lung diseases.

Inclusion Criteria

Able to give informed consent

My lung cancer is in an early stage and can be removed with surgery.

My heart and lungs are strong enough for lung surgery, as confirmed by my surgeon.

Exclusion Criteria

You have had allergic reactions to antibodies or NSO derived products in the past.

Pregnant or nursing

Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an i.v. infusion of IRDye800CW-nimotuzumab followed by lung cancer resection surgery

1-7 days

Multiple visits for infusion and surgery

Follow-up

Participants are monitored for adverse events and safety until day 30 post administration

30 days

What Are the Treatments Tested in This Trial?

Interventions

• IRDye800CW-nimotuzumab

Trial Overview The study tests IRDye800CW-nimotuzumab as a probe during lung cancer surgery. It's designed to bind to cancer cells making them visible under near-infrared light which may help surgeons remove the tumor more effectively. The trial aims to find the safest dose and best timing for imaging.

How Is the Trial Designed?

Group I: Optimal dose late time Experimental Treatment 1 Intervention

Participants will receive an i.v. infusion of 50 or 100 mg IRDye800CW-nimotuzumab (depending on cohorts 1 and 2). Participants will undergo lung cancer resection surgery 7+ days after infusion. Vitals, blood sample and urine sample will be collected before infusion for a baseline. Blood and vitals will be taken post infusion. Blood and urine samples will be collected on the day of surgery. Participants will be followed up for any adverse event until day 30 post administration

Group II: Optimal dose early time Experimental Treatment 1 Intervention

Participants will receive an i.v. infusion of 50 or 100 mg IRDye800CW-nimotuzumab (depending on results from cohorts 1 and 2). Participants will undergo lung cancer resection surgery 1-3 days after infusion. Vitals, blood sample and urine sample will be collected before infusion for a baseline. Blood and vitals will be taken post infusion. Blood and urine samples will be collected on the day of surgery. Participants will be followed up for any adverse event until day 30 post administration

Group III: Low dose intermediate time Experimental Treatment 1 Intervention

Participants will receive an i.v. infusion of 50 mg IRDye800CW-nimotuzumab. Participants will undergo lung cancer resection surgery 4-6 days after infusion. Vitals, blood sample and urine sample will be collected before infusion for a baseline. Blood and vitals will be taken post infusion. Blood and urine samples will be collected on the day of surgery. Participants will be followed up for any adverse event until day 30 post administration

Group IV: High dose intermediate time Experimental Treatment 1 Intervention

Participants will receive an i.v. infusion of 100 mg IRDye800CW-nimotuzumab. Participants will undergo lung cancer resection surgery 4-6 days after infusion. Vitals, blood sample and urine sample will be collected before infusion for a baseline. Blood and vitals will be taken post infusion. Blood and urine samples will be collected on the day of surgery. 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+

Western Economic Diversification Canada

Collaborator

Trials

2

Recruited

40+

Published Research Related to This Trial

The Fab2 fragment of the anti-EGFR antibody nimotuzumab, when labeled with IRDye800CW, showed faster tumor accumulation and clearance in mice compared to the full IgG version, allowing for quicker imaging results.

This new imaging probe provides a higher signal-to-background ratio within a shorter time frame (peaking at 2 hours post-injection), which can reduce patient wait times for imaging and potentially lower radiation exposure during procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of nimotuzumab Fab2 as an optical imaging agent in EGFR positive cancers. Bernhard, W., Barreto, K., Toledo, D., et al.[2023]

Nimotuzumab, a monoclonal antibody targeting the EGF receptor, was successfully radiolabeled with (177)Lu, showing optimal stability and specific binding to EGF-R positive cancer cells in vitro and in vivo.

Biodistribution studies in mice indicated that (177)Lu-DOTA-Nimotuzumab accumulates effectively in tumors over time, with significant tumor-to-muscle ratios, suggesting its potential as a targeted cancer therapy for EGF-R positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A potencial theranostic agent for EGF-R expression tumors: (177)Lu-DOTA-nimotuzumab. Calzada, V., Zhang, X., Fernandez, M., et al.[2021]

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]

The study developed a near-infrared fluorescent dye-labeled version of nimotuzumab, which showed equivalent binding to EGFR-positive cells compared to the original antibody, indicating its potential for targeted imaging in cancer surgery.

In mouse models, the fluorescent conjugate demonstrated significantly higher tumor uptake and lower liver accumulation compared to another EGFR-targeting antibody, suggesting it may be safer and more effective for image-guided surgical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Near infrared fluorescence imaging of EGFR expression in vivo using IRDye800CW-nimotuzumab. Bernhard, W., El-Sayed, A., Barreto, K., et al.[2019]

Nimotuzumab, a humanized monoclonal antibody targeting the EGFR, was successfully labeled with a radioactive compound ([99mTc(CO)3(H2O)3]+) with high yields of up to 90%, indicating effective preparation for further studies.

Biodistribution studies in normal mice showed that the labeled Nimotuzumab maintained over 90% stability after 24 hours, suggesting its potential as a reliable radiotracer for targeting EGFR in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of 99mTc-nimotuzumab with tricarbonyl ion: in vitro and in vivo studies. Garcia, MF., Camacho, X., Calzada, V., et al.[2019]

Nimotuzumab, an anti-EGFR monoclonal antibody, was found to be well-tolerated in 15 patients with advanced non-small cell lung cancer (NSCLC) when combined with palliative radiotherapy, showing a high disease control rate of 100% within the radiation field.

The most common side effects were mild lymphopenia and asthenia, with serious adverse events being rare; however, pneumonia with grade 4 neutropenia was noted at the 200mg dose, indicating the need for careful monitoring at this dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of nimotuzumab in combination with radiotherapy in stages IIB-IV non-small cell lung cancer unsuitable for radical therapy: Korean results. Choi, HJ., Sohn, JH., Lee, CG., et al.[2020]

Panitumumab-IRDye800 has been developed as an effective intraoperative optical imaging agent for detecting EGFR-expressing tumors, showing high specificity and sensitivity in various mouse models with different levels of EGFR expression.

The study demonstrated a strong correlation between the level of EGFR expression in tumors and the uptake of the panitumumab-IRDye800, indicating its potential for precise tumor visualization during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of panitumumab-IRDye800 conjugate as a fluorescence imaging probe for EGFR-expressing cancers. Bhattacharyya, S., Patel, N., Wei, L., et al.[2020]

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 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]

In a study of 37 patients with advanced non-small cell lung cancer (NSCLC), the combination of nimotuzumab and chemotherapy resulted in a response rate of 27% and a clinical benefit rate of 70.3%, indicating that this treatment can be effective for some patients.

The treatment was generally well tolerated, with the main side effects being bone marrow suppression and gastrointestinal reactions, suggesting that nimotuzumab can be a safe option when combined with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer]. Li, LF., Wang, HQ., Liu, XM., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04459065

Evaluation of IRDye800CW-nimotuzumab in Lung Cancer ... The purpose of this study is to determine the safety, optimal dose and imaging time of the investigational product, IRDye800CW-nimotuzumab for use as a near ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7953729/

Pre-clinical study of IRDye800CW-nimotuzumab ... We show preclinical studies demonstrating that nimotuzumab conjugated to IRDye800CW is safe and does not exhibit toxicities commonly associated with EGFR ...

3. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT04459065?keyword=%22Nimotuzumab%22

Evaluation of IRDye800CW-nimotuzumab in Lung Cancer ... IRDye800CW-nimotuzumab targets cancer cells over-expressing EGFR, allowing tumors to be visualized and may help surgeons better identify cancer during surgery.

4. oncotarget.com oncotarget.com/article/23557/text/

Near infrared fluorescence imaging of EGFR expression in ... This study shows that nimotuzumab is a good candidate for NIR fluorescent imaging and image-guided surgery.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11367928/

Study protocol for Near-infrared molecular imaging for lung ... This study is defined as an open-label, single-arm, single-stage phase II trial evaluating the effectiveness of Cetuximab-IRDye800CW in detecting tumors and ...

6. app.trialscreen.org app.trialscreen.org/trials/phase-1-2-lung-cancer-evaluation-irdye800cw-nimotuzumab-surgery-trial-nct04459065

Evaluation of IRDye800CW-nimotuzumab in Lung Cancer ... Participation in this study may help surgeons better identify and remove your lung cancer tumor during surgery, potentially improving the chances of successful ...

7. clinconnect.io clinconnect.io/trials/NCT04459065

Evaluation of IRDye800CW-nimotuzumab in Lung Cancer The purpose of this study is to determine the safety, optimal dose and imaging time of the investigational product, IRDye800CW-nimotuzumab for use as a near ...