Canakinumab in combination with docetaxel compared with docetaxel alone for the treatment of advanced non-small cell lung cancer following platinum-based doublet chemotherapy and immunotherapy (CANOPY-2): A multicenter, randomized, double-blind, phase 3 trial.

Canakinumab, an interleukin-1 beta inhibitor, previously showed reduced lung cancer incidence and mortality (CANTOS). Here, we compare the efficacy/safety of canakinumab versus placebo in patients with advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based doublet chemotherapy (PDC) and immunotherapy. CANOPY-2, a randomized, double-blind, phase 3 trial, enrolled adult patients with stage IIIB/IV NSCLC, without EGFR or ALK alterations, who had received one prior PDC regimen and one prior programmed death-1/programmed death-ligand 1 inhibitor and experienced subsequent disease progression. Patients were randomized to canakinumab plus docetaxel or placebo plus docetaxel. A total of 237 patients were randomly allocated: 120 (51 %) to canakinumab and 117 (49 %) to placebo, stratified by histology and prior lines of therapy. Three patients in the placebo arm did not receive study treatment. The trial did not meet its primary endpoint of overall survival: median 10.6 months (95 % confidence interval [CI], 8.2-12.4) for the canakinumab arm and 11.3 months (95 % CI, 8.5-13.8) for the placebo arm (hazard ratio, 1.06 [95 % CI, 0.76-1.48]; one-sided P-value = 0.633). AEs (any grade) were reported in 95 % of patients in the canakinumab group and in 98 % of patients in the placebo group. Grade 3-4 AEs were experienced by 62 % and 64 % of patients in the canakinumab and placebo groups, respectively, and grade 5 AEs were experienced by 8 % and 5 %. Prespecified, post-hoc subgroup analyses showed that patients with undetected circulating tumor DNA (ctDNA) and/or lower levels (< 10 mg/L) of C-reactive protein (CRP) achieved longer progression-free and overall survival than those with detected ctDNA or higher (≥ 10 mg/L) CRP levels. There was no association with treatment arm. Adding canakinumab to docetaxel did not provide additional benefit for patients with advanced NSCLC who had progressed after PDC and immunotherapy. NCT03626545.

Informations de copyright

Copyright © 2024 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest Luis Paz-Ares reports grants from AstraZeneca, Bristol Myers Squibb, Merck, and Pfizer; consulting fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, GlaxoSmithKline, Ipsen, Janssen, Lilly, Merck, Mirati, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, and Takeda; speaker honoraria from AstraZeneca, Janssen, Merck, and Mirati; leadership roles in Altum Sequencing and Genomica, all outside the submitted work. Yasushi Goto reports clinical trial grants from AZK and Pfizer; institutional grants from AbbVie, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Kyorin, Novartis, Ono Pharmaceutical, and Pfizer; speaker honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant Health Inc., Illumina, Merck, Novartis, Ono Pharmaceutical, Pfizer, and Taiho; leadership roles in Cancer Net Japan and JAMT, all outside the submitted work. Darren Lim reports grants from Bristol Myers Squibb; speaker honoraria from Boehringer Ingelheim, Merck, and Roche; and support for attending meetings from AstraZeneca and Taiho Pharmaceuticals, all outside the submitted work. Balazs Halmos reports research funding and honoraria for steering committee work from Novartis during the conduct of the study; reports grants from AbbVie, Advaxis, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Janssen, Merck, and Pfizer; consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Genentech, Janssen, Merck, Pfizer, Takeda, and Veracyte; and participation in advisory board meetings for Apollomics and TPT, all outside the submitted work. Byoung Chul Cho reports research funding from AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Champions Oncology, Dizal Pharma, Dong-A ST, Eli Lilly, GI Innovation, Interpark Bio Convergence Corp., Janssen, MedPacto, Merck, MOGAN Institute, Novartis, Ono Pharmaceutical, and Yuhan; royalties from Champions Oncology; consulting fees from AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, MedPacto, Merck, Novartis, Ono Pharmaceutical, Pfizer, Roche, Takeda, and Yuhan; participation in advisory board meetings for Bridgebio Therapeutics, Cyrus Therapeutics, Guardant Health, Joseah BIO, and KANAPH Therapeutics Inc.; stock ownership of Bridgebio Therapeutics, Cyrus Therapeutics, Gencurix Inc., Interpark Bio Convergence Corp., KANAPH Therapeutics Inc., and TheraCanVac Inc.; is a board of director for Gencurix Inc. and Interpark Bio Convergence Corp.; and is a founder of DAAN Biotherapeutics, all outside the submitted work. José Luis González Larriba reports consulting fees from Boehringer Ingelheim, Bristol Myers Squibb, Janssen, and Merck; speaker honoraria from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Janssen, Merck, Novartis, Pfizer, and Roche; and support for attending meetings from Bristol Myers Squibb, Janssen, Merck, Pfizer, Roche, and Takeda, all outside the submitted work. Caicun Zhou reports speaker honoraria from Amoy Diagnostics, Boehringer Ingelheim, C-stone, Eli Lilly, LUYE Pharma, Merck, Qilu, Roche, and Sanofi; and speaker and advisor fees from Hengrui, Innovent Biologics and TopAlliance Biosciences Inc., all outside the submitted work. Ingel Demedts reports consultancy and speaker honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck, and Roche, outside the submitted work. Jincheng Wu, David Demanse, and Bharani Dharan are Novartis employees. Bijoyesh Mookerjee, Socorro Portella, and Zewen Zhu were Novartis employees at the time the study was conducted. Martin Reck reports consulting fees, speaker honoraria and support for attending meetings from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Mirati Therapeutics, Novartis, Pfizer, Sanofi, and Roche; and participation in advisory board meetings for Sanofi, all outside of submitted work. Manuel Cobo, Akin Atmaca, and Sofia Baka declare no competing interests.