DISCERN: Dual Versus Single ICB in PDL-1 Negative NSCLC

Inclusion Criteria

• •1. Provision of signed and dated informed consent form.
• •2. Stated willingness to comply with all study procedures and availability for the duration of the study.
• •3. Male or female aged 18 years or older.
• •4. Participants must have histologically or cytologically confirmed non-small cell lung cancer which is stage IV
• •5. Participants should not have a known sensitizing mutation for which an FDA-approved.
• •targeted therapy for NSCLC exists in first line (e.g., EGFR, ALK, ROS1, BRAF, RET, NTRK, and MET sensitizing mutations
• •6. Participants should not have received prior systemic anticancer therapy for advanced or metastatic disease. For patients who are recently diagnosed and received one cycle of chemotherapy while awaiting NGS/PDL-1 testing are allowed on study after discussion with medical monitor.
• •7. Participants should have measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• •8. Participants should have a life expectancy of at least 3 months.
• •9. Participants should have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
• •10. Participants should have provided tumor tissue from locations not radiated prior to biopsy; fresh formalin fixed specimens or archival samples which have been determined as PD-L1 status \<1% or negative prior to randomization.
• •11. Participants should have been evaluated for circulating tumor DNA at baseline which has been determined to be detected, present or positive.
• •13. Participants should have adequate organ function to be able to safely receive the approved standard of care regimens per the current FDA approved package insert, treating investigators discretion and institutional guidelines.
• •14. For females of reproductive potential: Negative urine and serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, serum pregnancy test will be required. Participants should be willing to use an adequate method of contraception for the course of the study through 120 days after last dose of study medication or through 180 days after last dose of chemotherapeutic agents. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• •15. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.