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

Nivolumab is a PD-1 inhibitor that has demonstrated durable responses and improved survival in patients (pts) with previously treated, metastatic non-small-cell lung cancer (NSCLC). This is the first report of neoadjuvant PD-1 blockade in pts with early stage NSCLC. Pts with untreated, resectable, stage I-IIIA NSCLC underwent pretreatment tumor biopsy and then received two doses of nivolumab 3mg/kg administered at 4 and 2 weeks prior to surgical resection. Postoperatively, standard adjuvant chemotherapy was administered at investigator discretion. The primary endpoints were safety and feasibility of preoperative nivolumab administration. Exploratory endpoints included the degree of pathologic regression, as well as molecular and immunophenotypic changes in tumor and peripheral blood, including T cell repertoire analysis by TCR CDR3 deep sequencing, function, gene expression profiling, and tumor antigen recognition. An initial 6-patient safety run-in cohort was followed by an expansion cohort, with a planned accrual of 16 resected pts. As of 09/19/2016, 18 pts were enrolled and 16 completed surgical resection (two patients were not ultimately resected). No delays to surgery or surgical complications related to nivolumab occurred. Twelve of 15 resected patients (80%) had pathologic evidence of tumor regression, and 6 (40%) achieved major pathologic responses (MPR; <10% residual viable tumor), at the time of abstract submission final pathology was pending from the 16th resected pt. Of the 6 MPR pts, 3 had no radiographic evidence of response. Surgical specimens in all cases were characterized by substantial T cell infiltration. Among 6 MPRs, 4 tumors have been tested with PD-L1 IHC (28-8 assay) and 3 were positive. Both unique and shared T cell clones were expanded in both tumor and peripheral blood, including new infiltration of T cell clones found only in the post-treatment tumor specimen. Neoadjuvant nivolumab was feasible and safe. Most pts have pathologic evidence of anti-tumor response, including MPR in 6 of 15 pts. Neoadjuvant anti-PD1 immunotherapy may have substantial anti-tumor activity in early stage NSCLC.