Risk-adapted, Proteomic-guided Systemic Therapy for Previously Untreated Advanced Non-small Cell Lung Cancer

Inclusion Criteria:

* Participants must have histologically confirmed non-small cell lung cancer that is metastatic or unresectable (stage IIIC or IV), deemed appropriate to receive standard of care immune checkpoint inhibitor-based therapy given with palliative intent.
* Age ≥18 years at the time of consent.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥50%).
* Ability to understand and willingness to sign the informed consent form (ICF).
* Stated ability and willingness to adhere to all protocol requirements while on study

Exclusion Criteria:

* Tumor with known sensitizing alteration in ALK, EGFR, HER2, MET exon 14, NTRK, RET, or ROS1.
* Medical comorbidities precluding immune checkpoint inhibitor-based therapy per treating investgator's discretion.
* Previous systemic therapy for metastatic Stage IIIC or IV NSCLC. Patients who previously completed systemic therapy for early stage or locally advanced NSCLC ≥ 80 days prior to trial registration are eligible for inclusion.
* Any condition that in the opinion of the investigator would interfere with the participant's safety or compliance while on study