Abstract CT287: CANOPY-A: A phase III, multicenter, randomized trial evaluating canakinumab versus placebo as adjuvant therapy in patients with completely resected non-small cell lung cancer (NSCLC)
Authors: Garon Edward B. , Ardizzoni Andrea , Barlesi Fabrice , Cho Byoung Chul , De Marchi Pedro , Goto Yasushi , Kowalski Dariusz , Lu Shun , Paz-Ares Luis , Spigel David R. , Spira Alexander , Thomas Michael , Leung Mimi , Baum Jason , Zhu Zewen , Mookerjee Bijoyesh , Yang James Chih-Hsin 
Published: September 2020

Abstract
Background: In the CANTOS study, treatment with canakinumab (selective IL-1β inhibitor) was associated with reduced incidence and mortality of NSCLC in patients with stable post-myocardial infarction who had elevated high-sensitivity C-reactive protein (hs-CRP) levels. The results provided a rationale to investigate the therapeutic role of canakinumab in NSCLC. Methods: The phase III, multicenter, randomized, double-blind, placebo-controlled CANOPY-A study (NCT03447769) is evaluating the efficacy and safety of canakinumab as adjuvant therapy in adult patients with completely resected NSCLC. Patients with AJCC/UICC v.8 stages II-IIIA and IIIB (T&gt;5 cm, N2), any histology, completely resected (R0) NSCLC who have completed adjuvant cisplatin-based chemotherapy (≥2 cycles) and radiation therapy (if applicable) are eligible. Patients must not have had prior neoadjuvant chemotherapy or neoadjuvant radiotherapy. Patients (~1500) are randomized 1:1 to receive canakinumab (200 mg Q3W, SC) or placebo (Q3W, SC) for 18 cycles or until NSCLC disease recurrence as determined by investigator, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or patient, start of a new antineoplastic therapy, death, or loss to follow-up. Randomization is stratified by AJCC/UICC v.8 stage (IIA vs IIB vs IIIA vs IIIB with T&gt;5 cm, N2 disease), tumor histology (squamous vs non-squamous), and region (western Europe and North America vs eastern Asia vs rest of the world). Primary objective is disease-free survival (DFS) per local investigator assessment. Secondary objectives are overall survival (OS), lung cancer specific survival, safety, pharmacokinetics, immunogenicity, and patient reported outcomes. Adult patients with stage IIA-IIIA, IIIB (N2 disease only) NSCLC who are candidates for complete resection surgery (and therefore prospective candidates for the main study) will be asked to participate in a biomarker sub-study to understand how resection surgery may impact biomarkers involved in the IL-1β inflammatory pathway as well as mutations present in blood. For all patients participating into the sub-study, the levels of hs-CRP, other cytokines, and additional biomarkers in blood will be assessed at pre- and post-surgery (endpoint: summary statistics of hs-CRP and other pharmacodynamics [PD] biomarkers). For patients who will also enroll into the main study, possible associations between pre- and post-surgery biomarker levels with canakinumab efficacy will be determined (endpoint: DFS and OS by hs-CRP and other PD biomarkers). The CANOPY-A study is currently enrolling. As of Jan 13, 2020, there are 307 study locations.
Citation Format: Edward B. Garon, Andrea Ardizzoni, Fabrice Barlesi, Byoung Chul Cho, Pedro De Marchi, Yasushi Goto, Dariusz Kowalski, Shun Lu, Luis Paz-Ares, David R. Spigel, Alexander Spira, Michael Thomas, Mimi Leung, Jason Baum, Zewen Zhu, Bijoyesh Mookerjee, James Chih-Hsin Yang. CANOPY-A: A phase III, multicenter, randomized trial evaluating canakinumab versus placebo as adjuvant therapy in patients with completely resected non-small cell lung cancer (NSCLC) [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 CT287.