LBA49 - CANOPY-A: Phase III study of canakinumab (CAN) as adjuvant therapy in patients (pts) with completely resected non-small cell lung cancer (NSCLC)

Background

CAN is a high-affinity anti-IL–1β antibody that was superior to placebo (PBO) at preventing cardiac adverse events (AEs) in the CANTOS study. In an exploratory analysis of CANTOS, CAN was associated with significant reductions in NSCLC incidence and mortality, suggesting that CAN inhibition of the IL-1β pathway may have reduced the rate of progression, invasiveness, and metastatic spread of lung cancers undiagnosed at trial entry. Here, we show efficacy and safety of CAN as adjuvant therapy vs PBO in pts with completely resected NSCLC.

Methods

CANOPY-A (NCT03447769) is a Phase III study of adult pts with Stage II–IIIB (AJCC/UICC v8), completely resected NSCLC who had received adjuvant, cisplatin-based chemotherapy (CTx; if applicable) and thoracic radiotherapy (if applicable). Neoadjuvant CTx or chemoradiotherapy was not allowed. Pts were randomized 1:1 to receive CAN (200 mg) or PBO, subcutaneously, every 3 weeks for ≤18 cycles. Primary endpoint was disease-free survival (DFS); key secondary endpoint was overall survival (OS).

Results

At data cutoff (March 17, 2022), 1382 pts had been randomized to CAN (n=693) or PBO (n=689); baseline characteristics were generally balanced between arms. Median time from randomization to data cutoff was 18.9 months (mo; range 2.8–47.2); for DFS, there were 208 (30.0%) events with CAN and 218 (31.6%) with PBO. DFS was not significantly improved with CAN vs PBO (median 35.0 vs 29.7 mo; HR 0.94; 95% CI 0.78–1.14; one-sided p=0.258). Subgroup analyses (predefined based on demographics, baseline disease characteristics, and biomarkers) did not show any meaningful differences between the two arms for DFS. For OS, only to be formally tested if DFS was statistically significant, there were 44 (6.3%) events with CAN vs 56 (8.1%) with PBO. AEs were Grade ≥3 in 20.8% of pts in CAN arm vs 19.6% in PBO arm and AEs of any grade led to discontinuation in 4.3% of pts (CAN) vs 4.1% (PBO); on-treatment deaths occurred in 1.3% of pts (CAN) vs 2.3% (PBO).

Conclusions

CANOPY-A did not show a DFS benefit with CAN vs PBO after surgery and adjuvant CTx in pts with resected, Stage II–IIIB NSCLC. No new safety signals were identified with CAN treatment.

Clinical trial identification

CACZ885T2301/NCT03447769.

Editorial acknowledgement

Editorial assistance was provided by Alice Arcourt, PhD of Articulate Science Ltd, and was funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

E.B. Garon: Financial Interests, Personal, Advisory Board: Novartis, Merck, BMS, EMD Serono, Regeneron, Sanofi, Natera, Shionogi, ABL Bio, Xilio, GSK, Boehringer Ingelheim, Eisai, Gilead, Eli Lilly, Personalis; Financial Interests, Institutional, Invited Speaker: Novartis, Merck, EMD Serono, Eli Lilly, Genetech, Iovance, Neon, Mirati, AstraZeneca, BMS, ABL Bio; Non-Financial Interests, Advisory Role, Scientific Advisory Board: Lungevity. S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh, AstraZeneca, Roche; Financial Interests, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui Beigene, Roche, Hansoh. Y. Goto: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant Health Inc., Illumina, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho, Johnson and Johnson, D3bio; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, MSD, Merck, Novartis, Ono Pharmaceutical, Thermo Fischer, Pfizer, Taiho; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, DaiichiSankyo, Eli Lilly, Guardant Health, Preferred Network; Financial Interests, Personal and Institutional, Invited Speaker: Chugai, Pfizer, Novartis; Financial Interests, Institutional, Research Grant: Prefered Network. P.R. De Marchi: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb, Pfizer, Roche, Boheringer Igelheim, AstraZeneca, Bayer, MSD, Janssen, Amgen, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Sanofi, Roche, Janssen, Lilly; Financial Interests, Institutional, Invited Speaker: Bristol-Myers Squibb, Roche, Pfizer, Boheringer Ingelheim, Xcorery, MSD, IRX, AstraZeneca, Lilly. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, Beigene, Daichii, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-Cilag international NV, NOvartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President.ASEICA( Spanish Association of Cancer Research ): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. M. Thomas: Financial Interests, Personal, Advisory Board: Sanofi, Lilly, BMS, MSD, Roche, Boehringer, Janssen, AstraZeneca, Amgen, Novartis; Financial Interests, Personal, Invited Speaker: Sanofi, Lilly, MSD, Roche, GSK, Pfizer, Janssen, AstraZeneca, Amgen, Novartis; Financial Interests, Institutional, Advisory Board: Takeda; Financial Interests, Institutional, Invited Speaker: Takeda; Financial Interests, Institutional, Funding: Roche, Takeda, BMS, AstraZeneca, Amgen. J.C. Yang: Financial Interests, Institutional, Advisory Board: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Novartis, Bayer, GSK, Takeda Oncology, Puma Pharmaceuticals, Ono Pharmaceuticals, Merck Serono, MSD, Pfizer, Eli Lilly, Roche/Genentech, Janssen; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Novartis, AstraZeneca, MSD, Ipsen, Takeda Oncology; Financial Interests, Personal, Advisory Board: Yuhan Pharmaceuticals; Financial Interests, Invited Speaker: Dizal Pharmaceutical, Novartis, Numab, Merck, Daiichi Sankyo, Eli Lilly, Bayer, Janssen; Non-Financial Interests, Leadership Role, Board of Director: IASLC; Non-Financial Interests, Member: ASCO. A. Ardizzoni: Financial Interests, Personal, Invited Speaker, Occasional fees for advisory board participation and lectures: BMS; Financial Interests, Personal, Advisory Board, Occasional fees for advisory board participation: MSD, Takeda, Lilly, Bayer; Financial Interests, Personal, Advisory Board, Occasional fee for advisory board participation: Roche; Financial Interests, Personal, Advisory Board, Occasional fees for advisory board participation and lectures: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Financial support to my University for covering 50% costs of a no-profit accademic clinical trial: Ipsen. F. Barlesi: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd.. S. Khanna: Financial Interests, Personal, Full or part-time Employment: Novartis Pharma S.A.S. C. Bossen: Financial Interests, Institutional, Full or part-time Employment: Novartis Pharma AG. M. Carbini: Financial Interests, Institutional, Full or part-time Employment, Clinical Development Medical Director-Lung: Novartis; Financial Interests, Institutional, Stocks/Shares: Novartis. A. Yovine: Financial Interests, Institutional, Full or part-time Employment: Novartis. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines; Financial Interests, Personal, Advisory Board: Kanaph Therapeutic Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Joseah BIO; Financial Interests, Personal, Invited Speaker: Gencurix Inc, Interpark Bio Convergence Corp.; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, Kanaph Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Institutional, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp.; Other, Founder: DAAN Biotherapeutics. All other authors have declared no conflicts of interest.