Neoadjuvant anti-PD1, nivolumab, in early stage resectable non-small-cell lung cancer.

e20005 Background: Nivolumab is an anti-PD1 immune checkpoint blocker which has demonstrated durable responses and improved survival vs. second-line chemotherapy in metastatic non-small-cell lung cancer (NSCLC). This is the first report of anti-PD1/PD-L1 administration in early stage I-IIIA NSCLC as neoadjuvant therapy prior to surgical resection. Methods: Patients (pts) with resectable stage I-IIIA NSCLC underwent pretreatment tumor biopsy and then received 2 doses of nivolumab administered at 4 and 2 weeks prior to surgical resection. Postoperatively, standard adjuvant therapy was administered. The primary endpoint is safety and feasibility of anti-PD1 administration prior to surgery; exploratory endpoints include pathologic response and evaluation of changes in tumor and blood immune markers assessed by flow cytometry, immunohistochemistry and sequencing of tumor and T cell receptors in blood, tumor and draining lymph nodes. 16 pts in total will be enrolled. Results: Six pts have been enrolled to date. Results from the first three pts undergoing surgical resection after neoadjuvant nivolumab demonstrate no treatment-related toxicities or delays to surgery. Two of three patients had major radiologic and pathologic responses at the time of surgery including one pathologic complete response in an 8 cm squamous tumor. Resection specimens were characterized by brisk T cell infiltration, greater than seen in pre-treatment biopsies. Expansion of specific T cell clones was observed in both tumor and peripheral blood after nivolumab. Detailed genomic, immunologic and immunohistochemical analyses of pre- and post-treatment tissues are ongoing. Conclusions: Two of three pts with NSCLC receiving neoadjuvant nivolumab have had a major pathologic response to treatment at time of surgery. To date, preoperative nivolumab has been feasible with no toxicity-related delays to surgery or postoperative recovery. Intensive correlative analyses of pre- and post-treatment tissues are ongoing and will be reported. Clinical trial information: NCT02259621.