Canakinumab or Pembrolizumab as Monotherapy or in Combination as Neoadjuvant Therapy in Patients With Resectable Non-Small Cell Lung Cancer: CANOPY-N Trial

Background: Complete surgical resection is the standard treatment for patients with stage I-IIIA non-small cell lung cancer (NSCLC). Five-year survival rates in this population range from 19% to 50%, with most patients dying from distant recurrence. As neoadjuvant/adjuvant chemotherapy yields a modest 5% absolute overall survival benefit for these patients with NSCLC, new treatment options are needed. Preliminary data with PD-1 or PD-L1 inhibitors as neoadjuvant therapy have shown major pathologic responses (MPRs) or pathologic complete responses in patients with resectable NSCLC. In the CANTOS study, reduced incidence of NSCLC and decreased lung cancer–related mortality were observed in a dose-dependent manner in patients with atherosclerosis who received canakinumab (interleukin 1β inhibitor) versus those who received placebo. In preclinical NSCLC humanized models, treatment with canakinumab ± anti–PD-1 inhibitor has shown promising activity, and a synergistic effect was observed with this combination, which may enhance the efficacy of PD-1 inhibition by modulating pro-tumor inflammation in the tumor microenvironment. In this context, the CANOPY-N study was designed to evaluate the effect of canakinumab or pembrolizumab as monotherapy or in combination as neoadjuvant treatment for patients with resectable NSCLC. Methods: CANOPY-N (NCT03968419) is a Phase II, randomized, open-label study evaluating the effect of canakinumab or pembrolizumab as monotherapy or in combination as neoadjuvant treatment in patients with resectable NSCLC. Patients with histologically confirmed stage IB-IIIA NSCLC (excluding N2 and T4 tumors), no prior systemic therapy, Eastern Cooperative Oncology Group performance status 0 or 1, and eligibility for surgery with a planned resection in approximately 4-6 weeks after first dose of study treatment are eligible to participate. An archival (if obtained up to 6 months before first day of treatment) or new biopsy is required. Approximately 110 patients will be randomized in a 2:2:1 ratio (stratified by histology [squamous/nonsquamous]) to receive a total of 2 doses (200 mg every 3 weeks) 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. The primary endpoint is MPR rate (≤10% of residual viable tumor cells at time of surgery), and secondary endpoints include overall response rate per RECIST 1.1, MPR rate based on local assessment, surgical feasibility rates, safety, incidence of antidrug antibodies, pharmacokinetic parameters, and assessment of the relationship between blood- or tissue-based biomarkers and MPR. As of May 27, 2021, there are 44 active study locations. Citation Format: Jay M. Lee, Jean-Louis Pujol, Pilar Garrido, Edward S. Kim, Masahiro Tsuboi, Rafael Caparica Bitton, Jiawei Duan, Cecile Blin, Alexander Savchenko, Tony Mok. Canakinumab or Pembrolizumab as Monotherapy or in Combination as Neoadjuvant Therapy in Patients With Resectable Non-Small Cell Lung Cancer: CANOPY-N Trial [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA035.