MO01.23 Canakinumab or Pembrolizumab as Monotherapy or in Combination as Neoadjuvant Therapy in Patients with Surgically Resected Non-Small Cell Lung Cancer (NSCLC): CANOPY-N Trial

Complete surgical resection is the standard treatment for patients with stage I-IIIA non-small cell lung cancer (NSCLC). 5-year survival rates range from 19-50%, with most patients dying from distant recurrence. Neoadjuvant or adjuvant chemotherapy improves overall survival by only 5% in patients with NSCLC, and new treatment 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 patients with early stage NSCLC. CANTOS study demonstrated reduced incidence of NSCLC and decreased lung cancer-related mortality with canakinumab (an IL-1β inhibitor) versus placebo, in a dose-dependent manner for patients with atherosclerosis. In preclinical NSCLC humanized models, treatment with canakinumab with or without an anti PD-1 inhibitor demonstrated anti-tumor activity. Combination of canakinumab and pembrolizumab 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 canakinumab and pembrolizumab as monotherapy or in combination as neoadjuvant treatment for patients with resectable NSCLC. CANOPY-N (NCT03968419) is a phase II, randomized, open-label study evaluating effect of canakinumab or pembrolizumab monotherapy or in combination as neoadjuvant treatment in resectable NSCLC patients. Histologically confirmed stage IB-IIIA, treatment-naive, Eastern Cooperative Oncology Group performance status 0-1 NSCLC patients eligible for surgery and with a planned surgical resection in approximately 4-6 weeks (after 1 dose of study treatment), are eligible to participate. An archival (if obtained up to 6 months before 1 day of treatment) or new biopsy is required. Approximately 110 patients will be randomized in 2:2:1 ratio (stratified by histology [squamous/non-squamous]) to one of the treatment arms to receive a total of 2 doses (200 mg Q3w) of canakinumab alone (n = 44) or in combination with pembrolizumab (n = 44) or pembrolizumab alone (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 overall response rate, MPR rate based on local review, surgical feasibility rates, anti-drug antibodies incidence and pharmacokinetic parameters.