1194MO - Canakinumab (CAN) + docetaxel (DTX) for the second- or third-line (2/3L) treatment of advanced non-small cell lung cancer (NSCLC): CANOPY-2 phase III results

Background

In patients (pts) with advanced NSCLC who progress after platinum-doublet chemotherapy (PDC) and immune checkpoint inhibitor therapy, treatment options are limited; DTX is most commonly used in this setting. Preclinical data with CAN, a selective interleukin-1β inhibitor, plus DTX showed greater tumor growth reduction than DTX alone and decreased immunosuppressive cell infiltration in the tumor microenvironment.

Methods

The multicenter phase III CANOPY-2 trial (NCT03626545) evaluated CAN added to DTX in pts with advanced NSCLC. Eligible pts were ≥18 years old, with histologically confirmed stage IIIB-IV (AJCC v8) NSCLC without known EGFR or ALK alterations, who had received 1 prior PDC regimen and 1 prior anti-PD-(L)1 agent, combined or sequentially, for advanced disease. Pts were randomized to subcutaneous CAN 200 mg + intravenous DTX 75 mg/m² every 3 weeks or placebo (pbo) + DTX. The primary endpoint was overall survival (OS). Progression-free survival (PFS) was a secondary endpoint.

Results

Overall, 237 pts were randomized: 120 CAN + DTX, 117 pbo + DTX (3 pts did not receive pbo + DTX and were not included in safety analysis). As of Jan 8, 2021, median follow-up was 13.8 months (mo). Patient characteristics were well balanced between treatment arms. The primary endpoint of OS was not met (median 10.5 vs 11.3 mo for CAN vs pbo, respectively; HR 1.06; 95% CI, 0.76-1.48). Median PFS was 4.17 vs 4.21 mo for CAN vs pbo (HR 1.12; 95% CI, 0.85-1.50). Grade ≥3 adverse events (AEs) occurred in 70.0% of pts with CAN vs 69.3% with pbo, including infections in 21.7% vs 17.6% (6.7% vs 1.8% were fatal), neutropenia in 35.0% vs 38.6%, and thrombocytopenia in 3.3% vs 2.7% of pts, respectively. Study drug discontinuation due to AEs was reported in 23.3% vs 28.9% of pts receiving CAN vs pbo, respectively; on-treatment death in 35.8% vs 31.6% of pts.

Conclusions

Addition of CAN to DTX in the 2/3L setting did not improve OS or PFS in pts with advanced NSCLC. Safety profiles were comparable between the 2 arms, but a numerically higher incidence of infections (including fatal infections) occurred with CAN. Biomarker analysis is ongoing.

Clinical trial identification

NCT03626545.

Editorial acknowledgement

Medical editorial assistance was provided by Ana Costa, PhD of Chameleon Communications, London, UK, which was funded by Novartis, East Hanover, NJ, USA.

Legal entity responsible for the study

Novartis.

Funding

Novartis.

Disclosure

L. Paz-Ares: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AZ; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Mirati; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Member of the Board of Directors: Altum Sequencing; Financial Interests, Institutional, Other, Coordinating PI: Alkermes; Financial Interests, Institutional, Other, Coordinating PI: Amgen; Financial Interests, Institutional, Other, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Other, Coordinating PI: BMS; Financial Interests, Institutional, Other, Coordinating PI: Daiichi Sankyo; Financial Interests, Institutional, Other, Coordinating PI: IO Biotech; Financial Interests, Institutional, Other, Coordinating PI: Janssen-Cilag International NV; Financial Interests, Institutional, Other, Coordinating PI: Lilly; Financial Interests, Institutional, Other, Coordinating PI: Merck Sharp & Dohme Corp.; Financial Interests, Institutional, Other, Coordinating PI: Novartis; Financial Interests, Institutional, Other, Coordinating PI: Pfizer; Financial Interests, Institutional, Other, Coordinating PI: PharmaMar; Financial Interests, Institutional, Other, Coordinating PI: Roche; Financial Interests, Institutional, Other, Coordinating PI: Sanofi; Financial Interests, Institutional, Other, Coordinating PI: Takeda; Financial Interests, Institutional, Other, Coordinating PI: Tesaro. Y. Goto: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Guardant Health Inc.; Financial Interests, Personal, Advisory Board: Illumina; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Thermo Fischer; Non-Financial Interests, Institutional, Other, Local PI: AbbVie; Non-Financial Interests, Institutional, Other, Local PI: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Other, Coordinating PI: Chugai; Non-Financial Interests, Institutional, Other, Local PI: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Local PI: Eli Lilly; Financial Interests, Personal and Institutional, Other, Coordinating PI: Novartis; Financial Interests, Personal and Institutional, Other, Coordinating PI: Pfizer; Non-Financial Interests, Institutional, Research Grant: Preferred Network. W.D.T. Lim: Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Writing Engagements: Roche; Financial Interests, Institutional, Other, Trial Chair: Bristol Myers Squibb; Financial Interests, Institutional, Other, Grant funding for investigator-sponsored study: Bristol Myers Squibb; Financial Interests, Institutional, Other, Steering Committee Member: Novartis. B. Halmos: Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Mirati; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Advaxis; Financial Interests, Institutional, Research Grant: Blueprint; Financial Interests, Institutional, Research Grant: Elevation; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Personal, Other, Consulting: Merck; Financial Interests, Personal, Other, Consulting: BMS; Financial Interests, Personal, Other, Consulting: Novartis; Financial Interests, Personal, Other, Consulting: Boehringer Ingelheim; Financial Interests, Personal, Other, Consulting: AstraZeneca; Financial Interests, Personal, Other, Consulting: TPT; Financial Interests, Personal, Other, Consulting: Apollomics; Financial Interests, Personal, Other, Consulting: Pfizer; Financial Interests, Personal, Other, Consulting: Genentech; Financial Interests, Personal, Other, Consulting: Mirati. B.C. Cho: Financial Interests, Institutional, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal and Institutional, Research Grant: Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Board: Kanaph Therapeutics Inc., BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., BridgeBio Therapeutics, Kanaph Therapeutics Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Medpacto, Blueprint Medicines; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Non-Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. C. Zhou: Financial Interests, Personal, Invited Speaker: Lily China, Sanofi, BI, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone, Luye Pharma, Top-Alliance Biosciences Inc., Amoy Diagnostics; Financial Interests, Personal, Advisory Role: Innovent Biologics, Hengrui, Qilu, Top-Alliance Biosciences Inc. I. Demedts: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Takeda. A. Atmaca: Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Advisory Board: Novartis. S. Baka: Financial Interests, Personal, Principal Investigator: Novartis; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Principal Investigator: BMS; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Principal Investigator: Lilly. B.P. Mookerjee: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. S. Portella: Financial Interests, Personal, Full or part-time Employment: Novartis. Z. Zhu: Financial Interests, Personal, Full or part-time Employment: Novartis. B. Dharan: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Mirati, Merck, MSD, Novartis, Pfizer, Roche, Samsung Bioepis; Financial Interests, Personal, Other, Consultancy: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Mirati, Merck, MSD, Novartis, Pfizer, Roche, Samsung Bioepis. All other authors have declared no conflicts of interest.