Imaging Agent for Non-Small Cell Lung Cancer

Overseen By Nerissa T Viola, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nerissa T. Viola

Disqualifiers: Prior immunotherapy, Pregnant, Breastfeeding

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

Compensation: Varies

Number of Visits: 7

Duration: 6 weeks

6 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging agent to help detect and monitor non-small cell lung cancer (NSCLC) in patients who haven't yet received treatment. The imaging agent, [89Zr]Zr-DFO-emapalumab, is used during PET scans to assess how well a patient's cancer responds to their initial round of immunotherapy, which stimulates the immune system to fight cancer. Individuals diagnosed with NSCLC who haven't received immunotherapy may be suitable candidates, particularly if they have a tumor at least 2 cm in size that can be easily imaged. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new imaging agent.

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

The trial protocol does not specify if you need to stop your current medications. However, since the trial involves imaging and immunotherapy, it's best to discuss your current medications with the trial team.

What prior data suggests that this imaging agent is safe for use in humans?

Research has shown that similar imaging agents using zirconium-89, a radioactive element used in medical scans, are generally safe and practical. In studies involving patients with neuroendocrine cancer, these agents have been well-tolerated and show potential for use. However, specific safety information for the imaging agent [89Zr]Zr-DFO-emapalumab, being tested in this trial, is not yet available. As this is a Phase 1 trial, the primary goal is to assess safety, so researchers will closely monitor participants for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for non-small cell lung cancer, which primarily involve surgery, chemotherapy, radiation, and targeted therapy, [89Zr]Zr-DFO-emapalumab offers a novel approach as an imaging agent. This treatment uses a radiotracer, which helps doctors visualize cancer cells directly, providing a more precise understanding of the cancer's spread. Researchers are excited because it could lead to more accurate diagnoses and personalized treatment plans, potentially improving patient outcomes by targeting the cancer more effectively.

What evidence suggests that this imaging agent is effective for detecting non-small cell lung cancer?

Research has shown that [89Zr]Zr-DFO-emapalumab, the investigational imaging agent studied in this trial, is a promising tool for imaging non-small cell lung cancer (NSCLC). This method uses immuno-PET, which helps doctors see how well the drug targets cancer cells. The process involves a special marker, zirconium-89, that attaches to emapalumab, allowing doctors to view tumor sites and their response to treatment. Studies have demonstrated that zirconium-89 can effectively map cancer, making it valuable for detecting cancerous areas. Early tests in other cancers suggest this approach is safe and useful for monitoring how cancer responds to therapy. ^{1 4 5 6 7}

Who Is on the Research Team?

Nerissa T Viola, PhD

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with non-small cell lung cancer who haven't started treatment. They'll undergo PET scans using a new imaging agent before and after beginning immunotherapy to see how their tumors respond.

Inclusion Criteria

I had a PET scan within the last 2 months.

I can lie still for tests and fit into the scanning machine.

I have a tumor larger than 2 cm that can be seen on a PET scan.

Exclusion Criteria

Pregnant or breast feeding individuals

I haven't had immunotherapy for my current stage of lung cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Imaging

Participants undergo PET scans 1-2 hours post-tracer administration, again on the day following tracer administration, and 3-5 days after the tracer administration

2 weeks

Up to 6 visits (in-person)

Treatment

Participants receive immunotherapy and undergo PET imaging to assess response

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [89Zr]Zr-DFO-emapalumab

Trial Overview [89Zr]Zr-DFO-emapalumab, an experimental imaging agent, is being tested to visualize the immune response in lung cancer patients using PET scans before and about 30 days following the start of immunotherapy.

How Is the Trial Designed?

Group I: [89Zr]Zr-DFO-emapalumab Experimental Treatment 1 Intervention

Radiotracer \[89Zr\]Zr-DFO-emapalumab injection

Who Is Running the Clinical Trial?

Nerissa T. Viola

Lead Sponsor

Trials

1

Recruited

6+

Published Research Related to This Trial

89Zr-immuno-PET imaging can help identify cancer patients who are likely to respond to targeted therapies, potentially improving treatment outcomes by ensuring that only those who will benefit receive these therapies.

The use of 89Zr-immuno-PET in conjunction with antibody-drug conjugates (ADCs) allows for better prediction of drug delivery to tumors and helps optimize dosing regimens, enhancing the efficacy and safety of cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of Immuno-PET in Antibody-Drug Conjugate Development. Carmon, KS., Azhdarinia, A.[2019]

ZD1839, a targeted therapy that inhibits EGFR-associated tyrosine kinase activity, has shown efficacy in treating advanced non-small cell lung cancer (NSCLC) by disrupting tumor growth and survival mechanisms.

Clinical trials of ZD1839 not only assessed response rates but also focused on improving symptoms and quality of life for patients, highlighting its potential benefits beyond traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of epidermal growth factor receptor and symptom improvement in advanced non-small cell lung cancer. Natale, RB.[2005]

Ozoralizumab (OZR) is a novel TNF inhibitor that became the first variable heavy-chain antibody (VHH) drug approved for rheumatoid arthritis in September 2022, showcasing a unique structure with two anti-TNFα VHHs and one anti-HSA VHH.

Clinical data from the Phase II/III OHZORA trial indicate that OZR has favorable pharmacokinetics and efficacy in treating rheumatoid arthritis, along with a safety profile consistent with existing TNF inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structural, nonclinical, and clinical features of ozoralizumab: A novel tumour necrosis factor inhibitor. Takeuchi, T.[2023]

In a study involving 18 patients with advanced melanoma or non-small-cell lung cancer, the uptake of 89Zr-labeled pembrolizumab in tumors was found to correlate with treatment response and patient survival, suggesting it could be a useful predictor of therapy effectiveness.

The optimal dose for 89Zr-pembrolizumab was determined to be 5 mg, with the best imaging results observed on day 7 after administration, indicating a potential timeline for monitoring treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer. Kok, IC., Hooiveld, JS., van de Donk, PP., et al.[2022]

Fusarinine C (FSC) is a promising alternative to Desferrioxamine B (DFO) for radiolabeling biomolecules with zirconium-89, showing comparable efficiency and stability in PET imaging applications.

Radiolabeling at higher temperatures (85 °C) significantly improves tumor-to-organ ratios for both FSC and DFO conjugates, enhancing image contrast in microPET-CT imaging, which is crucial for accurate tumor visualization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclic versus Noncyclic Chelating Scaffold for 89Zr-Labeled ZEGFR:2377 Affibody Bioconjugates Targeting Epidermal Growth Factor Receptor Overexpression. Summer, D., Garousi, J., Oroujeni, M., et al.[2022]

The combination of ziv-aflibercept with cisplatin and pemetrexed showed an objective response rate of 26% and a median progression-free survival of 5 months in patients with non-small cell lung cancer, which aligns with historical data for first-line treatments.

However, the study was halted early due to a higher-than-expected incidence of reversible posterior leukoencephalopathy syndrome (RPLS), raising safety concerns that outweighed the treatment's efficacy, leading to the decision not to pursue further exploration of this combination in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II multicentre study of ziv-aflibercept in combination with cisplatin and pemetrexed in patients with previously untreated advanced/metastatic non-squamous non-small cell lung cancer. Chen, H., Modiano, MR., Neal, JW., et al.[2021]

In a 52-week study involving 140 patients with active rheumatoid arthritis, ozoralizumab at both 30 mg and 80 mg demonstrated significant clinical improvement, with high response rates maintained throughout the study period.

The treatment was well-tolerated, with no reported deaths and only 20 serious adverse events, although about 40% of patients developed antidrug antibodies, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of anti-TNF multivalent NANOBODY® compound 'ozoralizumab' without methotrexate co-administration in patients with active rheumatoid arthritis: A 52-week result of phase III, randomised, open-label trial (NATSUZORA trial). Tanaka, Y., Kawanishi, M., Nakanishi, M., et al.[2023]

In a 52-week study involving 381 patients with active rheumatoid arthritis, ozoralizumab at doses of 30 or 80 mg showed significant clinical improvement and high response rates according to the American College of Rheumatology criteria.

The treatment was well-tolerated, with serious adverse events occurring in only 23 patients, indicating a favorable safety profile throughout the study duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the anti-TNF multivalent NANOBODY® compound ozoralizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: A 52-week result of a Phase II/III study (OHZORA trial). Tanaka, Y., Kawanishi, M., Nakanishi, M., et al.[2023]

Ozoralizumab (OZR) demonstrated favorable pharmacokinetics with a long half-life of 18 days and a dose-dependent increase in plasma concentration, indicating effective dosing for rheumatoid arthritis treatment.

The study found that a trough concentration of approximately 1 μg/mL at week 16 correlated with better clinical outcomes, suggesting that maintaining this level may enhance treatment efficacy, although sustained efficacy was observed regardless of trough concentration by week 52.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and pharmacokinetics of ozoralizumab, an anti-TNFα NANOBODY® compound, in patients with rheumatoid arthritis: 52-week results from the OHZORA and NATSUZORA trials. Takeuchi, T., Chino, Y., Kawanishi, M., et al.[2023]

In a phase I study involving 33 patients with relapsed/refractory CD20+ non-Hodgkin's lymphoma, the combination of ipilimumab and rituximab showed manageable toxicity and a modest overall efficacy, with a 24% objective response rate and a median progression-free survival of 2.6 months.

Notably, patients with follicular lymphoma had a higher objective response rate of 58% and a median progression-free survival of 5.6 months, suggesting that the combination therapy may be particularly effective in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of the Combination of Rituximab and Ipilimumab in Patients with Relapsed/Refractory B-Cell Lymphoma. Tuscano, JM., Maverakis, E., Groshen, S., et al.[2020]

(89)Zr-based immuno-PET imaging is a promising technique for visualizing tumors and can help identify patients who may benefit from specific therapies, as well as monitor treatment outcomes.

Current research is focused on improving the production and bioconjugation methods of (89)Zr to enhance its effectiveness in clinical settings, with ongoing studies validating its use in predicting and tailoring cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zirconium-89 labeled antibodies: a new tool for molecular imaging in cancer patients. van de Watering, FC., Rijpkema, M., Perk, L., et al.[2022]

(89)Zr-immuno-PET is a promising imaging technique that can visualize and quantify the distribution of monoclonal antibodies (mAbs) in tumors, helping to predict their efficacy and toxicity based on initial clinical trials.

Initial studies have shown that (89)Zr-immuno-PET correlates with target expression levels in tumors, indicating its potential as a predictive biomarker for personalized treatment, particularly in HER2-positive breast cancer with trastuzumab-emtansine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immuno-Positron Emission Tomography with Zirconium-89-Labeled Monoclonal Antibodies in Oncology: What Can We Learn from Initial Clinical Trials? Jauw, YW., Menke-van der Houven van Oordt, CW., Hoekstra, OS., et al.[2022]

In a study involving 449 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab showed overall response rates of 15% at 2 mg/kg, 25% at 10 mg/kg every 3 weeks, and 21% at 10 mg/kg every 2 weeks, indicating that the 2 mg/kg dose may be sufficient for efficacy.

The analysis revealed no significant relationship between the dose of pembrolizumab and its efficacy or safety, suggesting that the lower dose of 2 mg/kg every 3 weeks is effective and safe for patients with previously treated advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer. Chatterjee, M., Turner, DC., Felip, E., et al.[2022]

ZD1839, an epidermal growth factor receptor (EGFR) inhibitor, has demonstrated effectiveness in treating advanced non-small cell lung cancer (NSCLC), showing improvements in symptoms and quality of life in two large phase II trials.

The ongoing research into ZD1839 and other EGFR inhibitors suggests they will play a significant role in NSCLC treatment, highlighting the need for healthcare professionals, especially nurses, to be informed about these emerging therapies for effective patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of clinical trials with epidermal growth factor receptor inhibitors in advanced non-small cell lung cancer. Thomas, M.[2019]

In a study of 32 patients with non-small-cell lung cancer (NSCLC) treated with ZD1839 for over 90 days, the drug achieved a disease control rate of 56.25%, with 18.75% experiencing partial remission.

ZD1839 was associated with manageable side effects, including acneiform rash (31.25%) and diarrhea (18.75%), but notably did not cause interstitial lung disease, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical observation of ZD1839 in treating 32 cases of non-small-cell lung cancer]. Zhang, L.[2018]

Citations

1. withpower.com withpower.com/trial/phase-1-carcinoma-non-small-cell-lung-5-2024-7dc30

Imaging Agent for Non-Small Cell Lung Cancer [89Zr]Zr-DFO-emapalumab is a promising drug because it uses a special imaging technique called immuno-PET to help doctors see how well the drug targets cancer ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38950555/

Imaging with [89Zr]Zr-DFO-SC16.56 anti-DLL3 ... - PubMed DLL3 PET-CT imaging of patients with neuroendocrine cancers is safe and feasible. These results show the potential utility of [ 89 Zr]Zr-DFO-SC16.56 for non- ...

3. mdpi.com mdpi.com/1422-0067/21/12/4309

Current Perspectives on 89 Zr-PET Imaging 89Zr is an emerging radionuclide that plays an essential role in immuno-positron emission tomography (PET) imaging. The long half-life of 89Zr (t1/2 = 3.3 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28821924/

89 Zr-labeled nivolumab for imaging of T-cell infiltration in a ... 89 Zr-Df-nivolumab was synthesized to map the biodistribution of PD-1-expressing tumor infiltrating T-cells in vivo using a humanized murine model of lung ...

5. researchgate.net researchgate.net/publication/329497456_Fully_automated_zirconium-89_labeling_and_purification_of_antibodies

Fully automated zirconium-89 labeling and purification of ... 89Zr as a promising radionuclide and it's applications for effective cancer imaging ... (89)Zr-DFO-mAb radioimmunoconjugate in a murine model of cancer.

6. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06439914/

Trial | NCT06439914 The goal of this clinical trial is to investigate the use of \[89Zr\]Zr-DFO-emapalumab as an IFN-γ PET imaging agent to detect lesions and response to ...

7. reporter.nih.gov reporter.nih.gov/search/GCtV6LXGoUKEhVf-TaP9GQ/project-details/10953760

RePORT ⟩ RePORTER We're sorry but RePORTER doesn't work properly without JavaScript enabled. Please enable it to continue.