Background: Pembrolizumab improves overall survival (OS) when added to platinum-based doublet chemotherapy (PDC) in patients with aNSCLC. However, progression-free survival (PFS) and OS remain disappointing for most patients and can vary depending on programmed death-ligand 1 (PD-L1) status. This highlights the need for additional therapeutic options. Canakinumab is a monoclonal anti-interleukin-1β antibody that inhibits pro-tumor inflammation and potentially enhances anti-tumor immune responses, with the potential to synergize with programmed death 1 inhibitors plus chemotherapy.

Methods: CANOPY-1 is a randomized, double-blind phase 3 study investigating the addition of canakinumab or placebo (PBO) to 1L pembrolizumab + PDC. Patients with previously untreated stage IIIB/C or IV NSCLC, of any histology and no known EGFR or ALK alterations, were randomized 1:1 and stratified based on PD-L1 status, geographic region, and histology to canakinumab 200 mg or PBO every 3 weeks, plus pembrolizumab and histology-guided PDC for 4 cycles, followed by maintenance canakinumab or PBO, with pembrolizumab ± pemetrexed. The primary endpoints were investigator-assessed PFS (Response Evaluation Criteria In Solid Tumors 1.1) and OS. Exploratory biomarker analyses were also investigated and will be presented at the time of the congress. The cut-off dates for these analyses were May 18, 2020 (PFS) and August 9, 2021 (OS).

Results: A total of 643 patients were randomized to canakinumab (n=320) or PBO (n=323) in combination with pembrolizumab + PDC. Baseline characteristics were well balanced across treatment arms. Median PFS was 6.8 months for both treatment arms (HR 0.85, 95% CI, 0.67-1.09; one-sided P=0.102). Median OS was 20.8 and 20.2 months for the canakinumab and PBO arms, respectively (HR 0.87, 95% CI, 0.70-1.10; one-sided P=0.123). Grade 3/4 adverse events (AEs) were reported for 205 (64.1%) patients in the canakinumab arm and 191 (59.3%) patients in the PBO arm, and fatal AEs were reported for 37 (11.6%) and 47 (14.6%) patients, respectively. AEs (any grade) leading to discontinuation of any study drug were reported for 72 (22.5%) patients in the canakinumab arm and 61 (18.9%) patients in the PBO arm.

Conclusions: The addition of canakinumab to pembrolizumab plus PDC did not statistically improve PFS nor OS for 1L treatment of patients with aNSCLC. No unexpected safety findings were observed with the addition of canakinumab to pembrolizumab plus PDC.

Citation Format: Daniel S. Tan, Enriqueta Felip, Gilberto Castro, Benjamin J. Solomon, Alastair Greystoke, Byoungchul Cho, Manuel Cobo, Tae Min Kim, Sandip Ganguly, Enric Carcereny, Luis Paz-Ares, Jaafar Bennouna, Marina Garassino, Michael Schenker, Sang-We Kim, Bijoyesh Mookerje, Vanessa Q. Passos, Stephanie Deudon, Bharani Dharan, Yuanbo Song, Rafael Caparica, Bruce E. Johnson. Canakinumab in combination with first-line (1L) pembrolizumab plus chemotherapy for advanced non-small cell lung cancer (aNSCLC): Results from the CANOPY-1 phase 3 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT037.