Canakinumab Combined with First-Line Pembrolizumab and Chemotherapy for Advanced NSCLC: CANOPY-1

Studies have shown that pembrolizumab improves overall survival (OS) when added to platinum-based doublet chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC).^1,2 However, the improvement in progression-free survival (PFS) and OS remains modest for most patients and can vary depending on the expression status of PD-L1.^1,2 This highlights the need for additional therapeutic options. Canakinumab is a monoclonal anti–interleukin-1β antibody that inhibits protumor inflammation and potentially enhances antitumor immune responses, with the potential to synergize with PD-1 inhibitors plus chemotherapy.

CANOPY-1 was a randomized, double-blind, phase 3 study that investigated the addition of canakinumab or placebo to pembrolizumab plus platinum-based doublet chemotherapy in the first-line setting. Patients with previously untreated stage IIIB/C or IV NSCLC of any histology and no known EGFR or ALK alterations were randomly assigned 1:1 and stratified based on PD-L1 status, geographic region, and histology to canakinumab 200 mg or placebo every 3 weeks, plus pembrolizumab and histology-guided platinum-based doublet chemotherapy for 4 cycles, followed by maintenance canakinumab or placebo, with pembrolizumab with or without pemetrexed. The primary end points were investigator-assessed PFS (RECIST version 1.1) and OS.²

A total of 643 patients were randomly assigned to canakinumab (n = 320) or placebo (n = 323) in combination with pembrolizumab plus platinum-based doublet chemotherapy; the baseline characteristics were well-balanced across treatment arms.²

The median PFS was 6.8 months for both treatment groups (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.67-1.09; 1-sided P = .102). Median OS was 20.8 months and 20.2 months for the canakinumab and placebo arms, respectively (HR, 0.87; 95% CI, 0.70-1.10; 1-sided P = .123).

Grade 3/4 adverse events (AEs) were observed in 205 (64.1%) patients in the canakinumab arm and 191 (59.3%) patients in the placebo arm. Fatal AEs were reported for 37 (11.6%) and 47 (14.6%) patients, respectively. AEs of 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 placebo arm.²

The researchers concluded that the addition of canakinumab to pembrolizumab plus platinum-based doublet chemotherapy was not associated with any new safety signals; however, the combination did not result in statistically improved PFS or OS in the first-line setting.

References

1. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378:2078-2092.
2. Tan D, Felip E, Castro G Jr, et al. 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. Presented at: 2022 American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract CT037.