PET/CT Imaging for Lung Cancer

Recruiting at 6 trial locations

Overseen By Alexander Shoushtari, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnant, Breastfeeding, Splenectomy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

5 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study to learn whether PET/CT (positron emission tomography/computed tomography) scans using an imaging agent (radiotracer) called zirconium Zr 89 crefmirlimab berdoxam is a safe and effective way to identify CD8+ T cells

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. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Zirconium Zr 89 crefmirlimab berdoxam for lung cancer?

Research shows that using zirconium-89 labeled antibodies in PET imaging can help predict which lung cancer patients will respond to treatments targeting the PD-1/PD-L1 pathway, which is important for immune system-based cancer therapies. This suggests that Zirconium Zr 89 crefmirlimab berdoxam might be effective in identifying patients who could benefit from such treatments. ^{1 2 3 4 5}

How does PET/CT imaging for lung cancer differ from other treatments?

PET/CT imaging for lung cancer using zirconium-89-labeled pembrolizumab is unique because it allows doctors to non-invasively assess how well a patient might respond to PD-1 antibody treatment, which is a type of immunotherapy. This imaging technique helps in predicting treatment effectiveness by visualizing the distribution and uptake of the drug in the body, which is not possible with conventional imaging methods. ^{1 2 6 7 8}

Research Team

Adam Schoenfeld, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with metastatic non-small cell lung cancer who haven't yet received engineered TIL cell therapy. Participants must consent to study requirements, use effective contraception, and not have a history of significant splenic dysfunction or be pregnant/breastfeeding.

Inclusion Criteria

I am 18 years old or older.

I have been diagnosed with metastatic non-small cell lung cancer.

Patient or legally authorized representative provided signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

Exclusion Criteria

I have had my spleen removed or have significant issues with my spleen.

Pregnant or breastfeeding women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive engineered tumor infiltrating lymphocyte (TIL) therapy and undergo PET/CT scans to assess CD8+ T cell distribution

2 weeks

Multiple visits for PET/CT scans and TIL therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Zirconium Zr 89 crefmirlimab berdoxam

Trial Overview The study tests if PET/CT scans using zirconium Zr 89 crefmirlimab berdoxam can safely and effectively detect CD8+ T cells in patients undergoing treatment for non-small cell lung cancer.

Participant Groups

Group I: Participants with Metastatic non-small cell lung cancer (NSCLC) Experimental Treatment 2 Interventions

Participants will have a diagnosis of metastatic non-small cell lung cancer (NSCLC)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

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]

The study demonstrated that [89Zr]-anti-PD-1 immuno-PET is a safe and effective imaging method to assess the response to PD-1 blockade in non-small cell lung cancer (NSCLC), showing higher uptake in responders compared to non-responders.

Conventional imaging methods like [18F]-FDG-PET were unable to detect the anti-tumor effects of PD-1 therapy, highlighting the potential of [89Zr]-anti-PD-1 as a more reliable tool for monitoring treatment response in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer. Puyalto, A., Rodríguez-Remírez, M., López, I., et al.[2023]

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]

Avelumab, an anti-PD-L1 antibody labeled with zirconium-89, showed high affinity for PD-L1 in cancer cells, indicating its potential for targeted cancer imaging and therapy.

In mouse models, the uptake of the labeled avelumab in PD-L1-expressing tumors increased with higher doses of unlabeled avelumab, suggesting that dose escalation can enhance targeting efficiency in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immuno-PET Imaging of the Programmed Cell Death-1 Ligand (PD-L1) Using a Zirconium-89 Labeled Therapeutic Antibody, Avelumab. Jagoda, EM., Vasalatiy, O., Basuli, F., et al.[2020]

89Zirconium-immuno-PET (89Zr-immuno-PET) can effectively assess tumor uptake of trastuzumab, showing that uptake increases with target concentration before plateauing, which is influenced by the total administered dose of the antibody.

The study highlights the importance of defining clinical target positivity cut-offs, as false-positive results can occur depending on the threshold used for immunohistochemistry scores, particularly when using a standard imaging dose of 50 mg of 89Zr-trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential and pitfalls of 89Zr-immuno-PET to assess target status: 89Zr-trastuzumab as an example. Huisman, MC., Menke-van der Houven van Oordt, CW., Zijlstra, JM., et al.[2021]

Immuno-PET using (89)Zr-labeled cmAb U36 demonstrated a sensitivity of 72% for detecting lymph node metastases in head and neck squamous cell carcinoma patients, outperforming conventional imaging methods like CT/MRI in certain aspects.

The accuracy of immuno-PET was 93% for detecting operated lymph node levels, indicating its potential as a reliable diagnostic tool for guiding treatment decisions in patients at high risk for metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients. Börjesson, PK., Jauw, YW., Boellaard, R., et al.[2015]

The monoclonal antibody ramucirumab (RAM) was successfully radiolabelled with zirconium-89, allowing for effective targeting and imaging of VEGFR2-positive tumors in prostate and ovarian cancer models.

In vivo studies demonstrated significant uptake of the radiolabelled RAM in tumors, with high tumor-to-muscle ratios observed over several days, indicating its potential for use in imaging and possibly treating angiogenesis-related cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of anti-VEGFR2 monoclonal antibody ramucirumab labelled with zirconium-89 for tumour imaging. Novy, Z., Janousek, J., Barta, P., et al.[2022]

In a pilot study of 10 patients with therapy-refractory interstitial pneumonitis treated with rituximab, PET/CT imaging using [89Zr]Zr-rituximab showed increased lung activity in four patients, suggesting potential for this imaging technique to predict treatment response.

One patient experienced a severe allergic reaction to the initial rituximab infusion, but subsequent imaging with [89Zr]Zr-rituximab was well-tolerated, indicating that this imaging method may be safe even after adverse reactions to the full drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[89Zr]Zr-rituximab PET/CT activity in patients with therapy refractory interstitial pneumonitis: a feasibility study. Adams, H., van de Garde, EM., van Moorsel, CH., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Application of Immuno-PET in Antibody-Drug Conjugate Development. [2019]

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

Immuno-PET Imaging of the Programmed Cell Death-1 Ligand (PD-L1) Using a Zirconium-89 Labeled Therapeutic Antibody, Avelumab. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Potential and pitfalls of 89Zr-immuno-PET to assess target status: 89Zr-trastuzumab as an example. [2021]

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

Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of anti-VEGFR2 monoclonal antibody ramucirumab labelled with zirconium-89 for tumour imaging. [2022]

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

[89Zr]Zr-rituximab PET/CT activity in patients with therapy refractory interstitial pneumonitis: a feasibility study. [2020]