TPS8122 Background: For patients (pts) with stage IIIA-IIIC NSCLC, though standard of care chemo-radiation (XRT) followed by 1 year of durvalumab has improved 5 year overall survival (OS), fewer than 50% survive 5 years. In this study, we adopted the established neoadjuvant chemotherapy (chemo) plus nivolumab (nivo) CheckMate-816 regimens for resectable stage I(>4cm)-IIIA yielding an increased complete pathologic response (pCR) rate and event free survival compared to chemo alone, as induction therapy in unresectable stage IIIA-IIIC NSCLC. The intent is to use induction chemo-nivo to treat pts traditionally considered unresectable (multi-station N2 or N3 disease) in order to downstage them enough to permit surgical resection. The study is structured to change (1) the immune checkpoint inhibitor (ICI) regimen to induction rather than consolidation which enables the chance to observe the systemic therapy’s efficacy, treat micro-metastatic disease earlier, and may decrease the morbidity of the ablative therapies (2) the ICI containing regimen by increasing from single agent ICI to combination chemo plus nivo which may improve systemic efficacy (3) the duration of treatment with pre and post ablative ICI containing therapy.Induction also provides a platform for studying tumor biology with the chance to discover surrogate markers of response and resistance to the induction regimen matched against response ahead of the definitive therapy. Methods: This is an investigator initiated trial for pts with newly diagnosed clinical stage IIIA-IIIC EGFR/ALK/ROS1 WT, SQ and NSQ NSCLC with PS 0-1. Pts must be able to tolerate surgery and have a primary tumor which is technically resectable with an N stage IIIA > 2 or more lymph node (LN) stations positive. Pts are treated with the same platinum doublet plus nivo regimens used in CheckMate-816 for 3 cycles followed by repeat CT and repeat biopsy of all LN stations biopsied at baseline and LN stations which at baseline had a high suspicion of harboring disease and which look technically unresectable. If the cancer is down-staged to a single LN station-N2, or is N1 or N0, the pt is offered surgery with an option of post-operative XRT. If not sufficiently down-staged, pts are treated with definitive chemo-nivo-XRT. All pts receive 1 year of consolidation nivo. The primary outcome is response to the induction regimen by repeat CT scan. Secondary outcomes include the rate of converting non-surgical stage III(A-C) to surgically resectable disease, pCR rate, extent of post-induction XRT field decrease, 2-year progression free survival, OS, quality of life, and exploratory outcomes include markers of resistance and response, and remote symptom monitoring. Enrolment will be 37 pts. The study is accruing with a plan to open at a second site. Clinical trial information: NCT06003075 .