Background: Patients (pts) with resectable stage IB (≥4cm)-IIIA non-small-cell lung cancer (NSCLC) derive modest overall survival benefit with neoadjuvant or postoperative adjuvant chemotherapy. Neoadjuvant therapy can speed the discovery of promising regimens by using pathologic response as a surrogate for OS. Major pathologic response (MPR), defined as < 10% viable tumor, was strongly associated with improved OS. PD-(L)1 checkpoint inhibitors in combination with chemotherapy are standard of care in advanced NSCLC. We hypothesize that the addition of N to neoadjuvant CP or CG will increase the MPR rate compared to historical controls. Methods: This is an investigator-initiated trial for pts with newly diagnosed AJCC 8^th stage IB (≥4cm)-IIIA squamous or non-squamous EGFR/ALK WT NSCLC with a plan to have surgery. Pts receive 3 courses of N 360mg IV q 3w added to C 75mg/m2 IV q 3w plus P 500 mg/m² IV q 3wks or G 1250mg/m² IV d1, d8 with surgery 3 wks after the last dose. The primary objective is MPR. To estimate pathologic response, the resected pathology specimens are cut >1 section/cm. Using the Aperio Digital scanning system©, slides were imaged, and then annotated by at least 2 pathologists for viable tumor vs. treatment effect with respective areas then automatically calculated and percentage of viable tumor calculated. Our primary endpoint will be reached if 10/34 (29%) planned pts have at least an MPR. Results: From 6/2018-8/2019, 13 pts were enrolled all of whom had surgery. Median age was 69 (49-80), 38% women, 31% nonsquamous, 54% stage IIIA, and 77% PD-L1 positive (≥1%, SP263). Pre-surgical grade 3 toxicity occurred in 2/13 pts, one of whom was changed to carboplatin for courses 2 and 3. Grade 3 toxicities were neutropenia (2/13), anemia (1/13), and renal (1/13). One pt. developed hypothyroidism 4 mos after surgery. One pt died 6 weeks after surgery from complications unrelated to study drugs. Our primary endpoint was met; 11/13 (85%), had at least an MPR with 6/13 (46%) and 5/13 (38%) having an MPR and pCR respectively. Radiologic response rate was 46% (PR 5, CR 1). Pts with either PD-L1+ or PD-L1- had MPRs. With a median follow-up of 10 months there are no recurrences. Conclusions: The combination of nivolumab added to platinum doublets was well tolerated. The primary endpoint of MPR in at least 10/34 pts was surpassed with MPR or pCR in 11/13 pts post-surgery. MPR was seen independent of PD-L1 score. Exploratory outcomes assessing markers of immune bias in tumor tissue and plasma are in process. Clinical trial information: NCT03366766