The study is a non-interventional evaluation of participants with extensive stage (ES) SCLC who will receive diagnostic and (where possible) post-progression tumor tissue profiling, alongside plasma ctDNA and CTC biomarker profiling during standard of care therapy in both first and second line treatment.

The following are the inclusion criteria. Participants are eligible to be included in this study only if all the following criteria apply. The participant has/is:

1. Histologically confirmed small cell lung cancer diagnosis
2. Diagnosis made with excisional or core needle biopsy specimen (fine needle aspirate may be permitted with approval from the Medical Monitor)
3. Subjects must submit tumor sample per the laboratory manual, defined as follows: 1L Cohort - Tissue obtained prior to the initiation of 1L therapy; 2L Cohort - Tissue obtained prior to the initiation of 1L therapy and/or a standard of care re-biopsy prior to the start of 2L therapy, if performed.
4. ECOG performance status of 0-2 at time of enrollment
5. For participants entering prior to first line therapy, planned extensive stage first-line therapy of etoposide plus platinum plus PD-L1 inhibitor (atezolizumab or durvalumab)
6. For participants entering post completion of standard of care first line prior to second line therapy, completion of an EP+CPI with or without maintenance therapy. Note: Participants who received 1L therapy that is not standard of care i.e., investigational therapy, are not eligible.
7. Extensive stage disease at time of diagnosis according to NCCN definition: Extensive Stage Small Cell Lung Cancer (SCLC) as either Stage IV disease (any T, any N, with M1a/b/c) or T3-4 disease due to multiple lung nodules that are too extensive or have a tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan (NCCN version 2.2026-September 16, 2025).
8. Willing and able to provide informed consent
9. Palliative radiotherapy is permitted as long as there is measurable disease outside of the radiotherapy port with which to assess response to therapy delivered

Participants will be excluded from the study if any of the following criteria apply. The participant has/is:

1. Patients with a secondary malignancy must have been both diagnosed > 3 years from the lung cancer of interest and have completed all therapy for that malignancy > 3 years prior to diagnosis of the lung cancer of interest, with the exception of the following:

   1. Patients with superficial basal cell carcinoma of low-risk histology per NCCN Guidelines (Low-risk histologic subtypes include nodular, superficial, and other non-aggressive growth patterns such as keratotic, infundibulocystic, and fibroepithelioma of Pinkus) and low-risk for recurrence per NCCN Guidelines (location on trunk or extremities, size < 2 cm, primary (not recurrent), with well-defined borders) can be included even if they are diagnosed < 3 years from the lung cancer of interest.
   2. Patients with superficial squamous cell carcinoma of low-risk pathology per NCCN Guidelines (verrucous, keratoacanthomatous) and low-risk for recurrence per NCCN Guidelines (located on trunk or extremities; ≤ 2 cm in size; primary lesion (vs. recurrent); well to moderately differentiated; < 2 mm thick and no invasion beyond subcutaneous fat; negative for perineural invasion; and negative for lymphatic or vascular involvement) can be included even if they are diagnosed < 3 years from the lung cancer of interest.

2. Mixed small cell and non-small cell histology

3. Small cell cancers of origin in other organs or suspected metastatic cancer from other sites (i.e., those without a known or suspected lung primary diagnosis)

4. Large Cell Neuroendocrine cancers

5. Carcinoids or atypical carcinoid tumors

6. Transformed small cell lung cancer emerging in the setting of targeted therapy for NSCLC

7. Treated with an investigational agent of another immunotherapy class (i.e., non PD-1 or PD-L1 inhibitor)

8. Not willing to have additional blood samples collected

This protocol targets patients with Extensive Stage (ES) Small Cell Lung Cancer (SCLC) receiving first-line and second-line standard of care therapy