Objectives: Complete surgical resection is the standard treatment (tx) for pts with stage I-IIIA NSCLC. 5-year survival rates range from 19-50%, with most pts dying from distant recurrence. Neoadjuvant or adjuvant chemotherapy improves overall survival (OS) by only 5% in pts with NSCLC, and new tx options are needed. Preliminary data with PD-1 or PD-L1 inhibitors as neoadjuvant therapy has shown major pathologic responses (MPR) or pathologic complete responses (pCR) in pts with early stage NSCLC. CANTOS study demonstrated reduced incidence of NSCLC and decreased lung cancer-related mortality with CAN (IL-1β inhibitor) versus placebo, in a dose-dependent manner for pts with atherosclerosis. In pre-clinical NSCLC humanized models, tx with CAN±anti PD-1 inhibitor could lead to anti-tumor activity. Combination of CAN and PEM is expected to enhance the efficacy of PD-1 inhibition by inhibiting dysregulated inflammation in tumor microenvironment. Based on available evidence, CANOPY-N study was designed to evaluate effect of CAN and PEM as monotherapy or in combination as neoadjuvant tx for pts with resectable NSCLC. Methods: CANOPY-N (NCT03968419) is a phase II, randomized, open-label study evaluating effect of CAN or PEM monotherapy or in combination as neoadjuvant tx in resectable NSCLC pts. Histologically confirmed stage IB-IIIA, tx-naive, ECOG PS 0-1 NSCLC pts eligible for surgery and with a planned surgical resection in approximately 4-6 weeks (after 1st dose of study tx), are eligible to participate. An archival (if obtained up to 6 months before 1st day of tx) or new biopsy is required. Approximately 110 pts will be randomized in 2:2:1 ratio (stratified by histology [squamous/non-squamous]) to one of the tx arms to receive a total of 2 doses (200 mg Q3w) of CAN alone (n=44) or in combination with PEM (n=44) or PEM (n=22) with safety follow-up up to 130 days from last study drug dose. Primary endpoint is to determine MPR rate (≤10% of residual viable tumor cells at time of surgery), secondary endpoints include determination of ORR, MPR rate based on local review, surgical feasibility rates, anti-drug antibodies incidence and PK parameters.

Citation Format: Jay M. Lee, Pilar Garrido, Edward S. Kim, Cagatay Arslan, Jean-Louis Pujol, Yuanbo Song, Cecile Blin, Vanessa Rodrik-Outmezguine, Bijoyesh Mookerjee, Vanessa Passos, Tony Mok. Randomized phase II study of canakinumab (CAN) or pembrolizumab (PEM) alone or in combination as neoadjuvant therapy in patients (Pts) with surgically resected (Stage IB-IIIA) non-small cell lung cancer (NSCLC): CANOPY-N [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT192.