Validation of the SPOT-MAS Lung Test Using Circulating Tumor DNA for the Detection of Lung Cancer

Multi-center Prospective Validation of the SPOT-MAS Lung Test Using Circulating Tumor DNA for the Detection of Lung Cancer

This is an observational clinical trial, aiming to evaluate the efficacy of the SPOTMAS LUNG (SML) test compared to Low dose CTScan (LDCT)/None contrast CTScan (NCCT) in two distinct risk populations:

• Cohort A: To demonstrate that SML is concordant with LDCT/NCCT in general population lung cancer screening, including low-risk (LRs0-1-2), intermediate-risk (LRs3), and high-risk (LRs4) groups.
• Cohort B: To validate the sensitivity and specificity of SML in the high-risk group (LRs4).

This is a prospective, multi-center cohort study to access the performance of SPOT-MAS Lung (SML) in two different scenarios: lung cancer screening (Cohort A) and lung cancer diagnosis (Cohort B).

Sample size and accuracy analyses were performed independently for the study objectives within each cohort. The minimum sample size for Cohort A is approximately 526 samples. Participants will be randomly selected from the screening population for this study without prior LDCT classification criteria. The minimum sample size for Cohort B is approximately 658 samples. Participants will be selected from individuals who have undergone LDCT/NCCT with LUNG-RADS 4 results.

Each Cohort A or B requires a 50% proportion of smokers and 50% of never-smokers or light-smokers, 10mL blood sample and LDCT/NCCT are collected.

Cohort A: According to current lung cancer screening and diagnosis guidelines, volunteers will undergo the following imaging methods:

Lung-RADS 3: Recommended to have a repeat LDCT after 6 and 12 months. Lung-RADS 0-1-2: Recommended to have a repeat LDCT after 12 months. Lung-RADS 4: Recommended to have contrast-enhanced computed tomography (CECT). Cohort B: According to current lung cancer screening and diagnosis guidelines, the Lung-RADS 4 group will be recommended for contrast-enhanced computed tomography (CECT).

Cohort A and B:

If CECT results show a lesion ≥8mm in the lung, biopsy is recommended, and histopathological results evaluated.

• If histopathology is malignant/confirms cancer: proceed with treatment. Treatment costs ARE NOT covered by the study.
• If histopathology is benign: repeat LDCT after 12 months. If CECT results show a lesion <8mm in the lung, or no lesion is seen in the lung, repeat LDCT after 12 months.

LDCT or CECT fee in Month 6 and Month 12 will be covered by this study.

Inclusion Criteria:

Cohort A

1. Volunteers (participants) aged 50-80 years at the time of consent.

   1. 50% smokers with a smoking history of 20 pack-years who currently smoke or have quit within the past 15 years.
   2. 50% never-smokers or light smokers (< 20 pack-years or quit > 15 years) who are first- or second-degree relatives of LC patients.

2. Willing to undergo LDCT/NCCT of the chest for lung cancer screening.

3. Willing to consent to an investigational blood draw during the index LDCT/NCCT screening visit and before any invasive procedures or treatment for lung cancer diagnosis.

4. Willing to consent to a 1-year follow-up and additional follow-ups as per protocol.

Cohort B

1. Subjects aged 50-80 years at the time of consent.

   1. 50% smokers with a smoking history of 20 pack-years who currently smoke or have quit within the past 15 years.
   2. 50% never-smokers or light smokers (< 20 pack-years or quit > 15 years) who are first- or second-degree relatives of LC patients.

2. Have undergone LDCT/NCCT of the chest for lung cancer screening/diagnosis, including only high-risk lesions (LUNG-RADS 4).

3. Willing to consent to an investigational blood draw before any invasive procedures (CECT/PET-CT/biopsy) or treatment for lung cancer diagnosis.

4. Willing to consent to a 1-year follow-up and additional follow-ups as per protocol.

Exclusion Criteria for both Cohort A and Cohort B

1. Subject has a health problem that substantially limits life expectancy and/or the ability or willingness to have curative lung surgery.

2. Subject is undergoing CECT for investigation of highly suspicious symptoms for lung cancer.

3. Pre-existing or history of lung cancer.

4. History of any malignancy (subjects who have undergone surgical removal of skin squamous cell cancer may be enrolled provided the procedure was completed at least 12 months prior to the date of provision of informed consent for the study).

5. Currently taking any anti-neoplastic or disease-modifying anti-rheumatic drugs.

6. Currently receiving treatment for pneumonia.

7. Any major physical trauma (e.g., disruption of tissue, surgery, organ transplant, blood product transfusion) within the 30 days leading up to the provision of informed consent.

8. Known medical condition which, in the opinion of the investigator, should preclude enrollment into the study.

9. Participation in a clinical research study in which an experimental medication and/or medical procedure has been administered or may be administered within the 30 days leading up to providing informed consent or may be administered through the time of subject screening.

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   Exclusion Criteria:

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