• Participants must meet ALL of the following criteria for inclusion in the study:

• Age ≥ 18 years old.

• Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.

• Pathologically confirmed stage IV NSCLC disease.

• Have acquired resistance to an immune checkpoint inhibitor, defined as disease progression immediately following an initial response or stable disease (≥ 6 months duration) to exactly 1 line of anti-PD-L1 or anti-CTLA-4 therapy (for Stage III, IV, or recurrent disease) that was given alone or in combination with chemotherapy.

• Participants with AGA must have 1 or more documented AGA(s): EGFR, ROS1, neurotrophic tyrosine receptor kinase (NTRK), B rapidly accelerated fibrosarcoma (BRAF), mesenchymal epithelial transition (MET) exon 14 skipping, rearranged during transfection (RET), Kirsten RAt sarcoma (KRAS).

• Participants with AGA must meet the following criteria for advanced or metastatic NSCLC. Participants who have been treated with 1 or 2 prior lines of applicable targeted therapy that is locally approved for the participant's genomic alteration at the time of screening:

∙ Participants who have tumors with EGFR L858R or exon 19 deletion mutations must have received prior Osimertinib.

‣ Participants who received a targeted agent as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose or received at least one additional course of targeted therapy for the same genomic alteration (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease.

‣ Participants who have been treated with a prior tyrosine kinase inhibitor (TKI) must receive additional approved targeted therapy, if locally available and clinically appropriate, for the applicable genomic alteration, or the participant will not be allowed in the study.

‣ Participants must meet the inclusion criteria #4 listed above.

• ECOG performance status of 0 to 2.

• Measurable tumor lesions according to RECIST v1.1. (at Baseline day 1).

• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.

⁃ Agreement to practice effective contraception for female participants of child-bearing potential and non-sterile males. Female participants of child-bearing potential must agree to use effective contraception for up to 7 months after completion of therapy, and non-sterile male participants must agree to use a condom for up to 7 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), orals, injectables, 2 forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and hormonal therapy.

⁃ Participants with known HIV infection must be receiving anti-retroviral therapy and have an undetectable viral load at their most recent viral load test within 6 months prior to enrollment.