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

This is a phase 2, pragmatic, 1:1 randomized, open-label study that evaluates risk-adapted, proteomic-guided systemic therapy to improve 12-month progression free survival (PFS) among patients with 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