CANOPY-N: A phase II study of canakinumab (CAN) or pembrolizumab (PEM), alone or in combination, as neoadjuvant therapy in patients (pts) with resectable stage Ib-IIIa non-small cell lung cancer (NSCLC)

ABSTRACT

Background: CAN is a monoclonal antibody that inhibits proinflammatory IL-1beta-driven pathways that may play a role in tumor growth in early-stage NSCLC. Preclinical data suggest targeting IL-1beta could decrease inflammation and immunosuppression in the tumor microenvironment (TME). Method(s) CANOPY-N (NCT03968419) is a phase II, randomized, open-label study of neoadjuvant CAN, PEM or CAN+PEM in resectable NSCLC. Eligibility Stage IB-IIIA NSCLC;treatment (tx) naive;ECOG PS 0-1;and eligible for planned resection 4-6 weeks after first dose. Pts were randomized 221 to the tx arms CAN, CAN+PEM or PEM. CAN and PEM were both given as two 200 mg doses once every 3 weeks. Primary endpoint major pathological response (MPR) rate based on central review. Key secondary endpoints overall response rate (ORR), surgical feasibility rate, and safety. Changes in CD8+ T cell, tumor-associated macrophage (TAM) and regulatory T cell (Treg) levels, among others, were assessed in exploratory biomarker analyses. Result(s) 88 pts enrolled across 3 arms CAN (n=35), CAN+PEM (n=35) and PEM (n=18). 87 pts completed planned neoadjuvant tx. Four pts did not have surgery 3 due to disease progression (CAN) and 1 to pt decision (CAN+PEM). MPR rates were 2.9% (CAN), 17.1% (CAN+PEM) and 11.1% (PEM). ORRs were 0% (CAN), 8.6% (CAN+PEM) and 11.1% (PEM). Gr >=3 AEs occurred in 37.1%, 28.6% and 22.2% of pts, of which 0%, 11.4% and 11.1% were tx related, in the CAN, CAN+PEM and PEM arms, respectively. Decreases in TAMs and Tregs were seen in CAN arms whereas increases in CD8+ T cells were seen in PEM arms. Modulations were more pronounced with CAN+PEM (Table). [Formula presented] Conclusion(s) CANOPY-N did not meet the primary endpoint of MPR rate, with minimal clinical efficacy and no increase in CD8+ T cells with CAN alone. No new safety signals were seen. IL-1beta inhibition impacted inflammation and immunosuppression in the TME. Clinical trial identification CACZ885V2201C / NCT03968419. Editorial acknowledgement Editorial assistance was provided by Ollie Butlin, MSc of Articulate Science Ltd., and was funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study Novartis Pharmaceuticals Corporation. Funding(s) Novartis Pharmaceuticals Corporation. Disclosure T.S.K. Mok Financial Interests, Personal, Invited Speaker AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Fishawack Facilitate, InMed Medical Communication, Lunit USA, Inc., Merck Serono, MSD, Roche, MD Health, Medscape/WebMD, PeerVoice, Touch Medical Media, Permanyer SL, Prime Oncology, Research to Practice, Sanofi-Aventis, Takeda, PER, Daz Group, Lucence Health Inc., Janssen Pharmaceutical NV, Jiahui Holdings Co., LiangYiHui Healthcare, Merck Pharmaceuticals HK Ltd, MiRXES, Novartis, OrigiMed Co. Ltd., Pfizer, Shanghai BeBirds Translation & Consulting Co., Ltd., Taiho Pharmaceutical Co., Ltd, AstraZeneca;Financial Interests, Personal, Advisory Board AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Blueprint Medicines, Berry Oncology, CStone Pharma, Daiichi Sankyo, Fishawack Facilitate, Eisai, Gritstone Oncology, Guardant Health, G1 Therapeutics, Hengrui, Ignyta, IQVIA, Incyte Corporation, Inivata, Janssen, Loxo Oncology, Qiming Dev., Lunit USA, Inc., Merck Serono, MSD, Roche, Mirati Therapeutics, MoreHealth, Novartis, OrigiMed, Puma Tech., Sanofi-Aventis, Takeda, Virtus Medical, Yuhan, Curio Science, Bayer Healthcare Pharmaceuticals Ltd., Covidien LP, C4 Therapeutics, Cirina Ltd., Da Volterrra, F. Hoffmann-La Roche Ltd / Genentech, Gilead Sciences, Lucence Health Inc., Medscape LLC / WebMD, MiRXES, OSE Immunotherapeutics, Pfizer, SFJ Pharmaceutical Ltd., Synergy Research, Tigermed, Vertex Pharmaceuticals, Berry Oncology, D3 Bio Ltd., Lakeshore Biotech;Financial Interests, Personal, Invited Speaker, Former known as Hutchison Chi-Med HutchMed;F nancial Interests, Personal, Officer, Chairman ACT Genomics-Sanomics Group;Financial Interests, Personal, Stocks/Shares Sanomics Ltd., Biolidics Ltd., Aurora Tele-Oncology, AstraZeneca;Financial Interests, Personal, Stocks/Shares, Former known as Hutchison Chi-Med HutchMed;Financial Interests, Institutional, Funding, For clinical trials performed at CUHK Merck Serono, AstraZeneca, BMS, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology;Non-Financial Interests, Personal, Advisory Role geneDecode;Non-Financial Interests, Personal, Other, Invited Speaker AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc., Sanomics Ltd.;Non-Financial Interests, Personal, Leadership Role, Term ended on 30 June 2022 American Society of Clinical Oncology (ASCO);Non-Financial Interests, Personal, Leadership Role Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen's College & Prep. School (Hong Kong);Non-Financial Interests, Personal, Leadership Role, Term ended Chinese Society of Clinical Oncology (CSCO);Non-Financial Interests, Personal, Leadership Role, Term ended on 30 April 2019 International Association for the Study of Lung Cancer (IASLC). M. Tsuboi Financial Interests, Personal, Invited Speaker, Lecture Johnson & Johnson Japan;Financial Interests, Personal, Advisory Board, Lectures, Advisory boards AstraZeneca KK, Chugai Pharmaceutical CO.,LTD, MSD;Financial Interests, Personal, Invited Speaker, Lectures Eli Lilly Japan, Bristol Myers Squibb KK, Teijin Pharma, Taiho Pharma, Medtronic Japan, ONO Pharmaceutical CO.,LTD;Financial Interests, Personal, Advisory Board, Advisory boards Novartis;Financial Interests, Personal, Invited Speaker Daiichi-Sankyo company limited, MSD, AstraZeneca, Novartis;Financial Interests, Institutional, Research Grant Beohringer-Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical CO.,LTD, Bristol Myers Squibb KK, Novartis;Financial Interests, Institutional, Invited Speaker Eli Lilly Japan. J.M. Lee Financial Interests, Personal, Advisory Board Bristol Myers Squibb, Astrazeneca, Roche/Genentech, Novartis;Financial nterests, Personal, Invited Speaker, LCMC3, LCMC4, NAUTIKA-1 Roche/Genentech;Financial Interests, Personal, Invited Speaker, CANOPY-N, GEOMETRY-1 Novartis. E.S. Kim Financial Interests, Personal, Other, Consulting/Research Regeneron, Takeda, Novartis. J. Zhang Financial Interests, Personal, Advisory Board AstraZeneca, Bayer, Biodesix, Bristol Myers Squibb, Cardinal Health, Daiichi Sankyo, Hengrui Therapeutics, Eli Lilly, Mirati, Nexus Health, Novartis, Novocure, Sanofi, Takeda Oncology;Financial Interests, Personal, Invited Speaker AstraZeneca, MJH Life Sciences, Regeneron, Sanofi;Financial Interests, Institutional, Research Grant, PI and Sponsor AstraZeneca, Biodesix, Nilogen, Genentech;Financial Interests, Institutional, Invited Speaker Hengrui Therapeutics, Mirati, Novartis, Abbvie, BeiGene, Merck;Financial Interests, Institutional, Research Grant, PI, basic science research Mirati;Non-Financial Interests, Personal, Member, American Society of Clinical Oncology ASCO;Non-Financial Interests, Personal, Member, American Association for Cancer Research AACR;Non-Financial Interests, Personal, Member, International Association for the Study of Lung Cancer IASLC;Non-Financial Interests, Personal, Member, Chinese American Hematologist and Oncologist Network CAHON. J. Duan Financial Interests, Personal, Stocks/Shares Novartis Pharmaceuticals Corporation. C. Lobetti-Bodoni Financial Interests, Personal, Full or part-time Employment, Clinical Development Medical Director Novartis Oncology;Financial Interests, Personal, Stocks/Shares Novartis Oncology;Other, Personal, Other, My husband is a Roche employer Roche;Other, Personal, Other, My husband had consultancy in the last two years with these companies Sanofi and Takeda;Other, Personal, Other, My husband ha honoraria in the last 2 years with these companies Takeda, Jansenn-Cilag Ltd;Other, Personal, Other, My husband owns stock of this company Harlock Helatcare Consulting Ltd. J.C. Brase Financial Interests, Personal, Full or part-time Employment Novartis;Financial Interests, Personal, Stocks/Shares Novartis. A. Savchenko Financial Interests, Personal, Full or part-time Employment Novartis;Financial Interests, Personal, Stocks/Shares Novartis. P. Garrido Lopez Financial Interests, Personal, Advisory Board Abbvie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, sanofi;Financial Interests, Personal, Invited Speaker AstraZeneca, Janssen, MSD, Novartis, Pfizer, Roche, Takeda, Novartis, IO Biotech;Financial Interests, Personal, Advisory Board, Spouse Boehringer Ingelheim, Gebro, Janssen, Nordic;Financial Interests, Personal, Invited Speaker, Spouse Boehringer Ingelheim, Janssen;Financial Interests, Personal, Other, Data monitoring committee for a clinical trial in 2020 Novartis;Financial Interests, Personal, Other, Lung Cancer Medical Education TASC Committee 2021 Janssen;Financial Interests, Institutional, Invited Speaker Novartis, Janssen, AstraZeneca, Pfizer, Blue print, Apollomics, Amgen, Array Biopharma;Financial Interests, Personal, Invited Speaker, study entitled JNJ-372 Janssen;Non-Financial Interests, Personal, Leadership Role, Council member as Women for Oncology Committee ChairFellowship and Award Committee and Press CommitteeFaculty for lung and other thoracic tumours ESMO;Non-Financial Interests, Personal, Leadership Role, President of the Spanish Federation of Medical Societies (FACME) FACME;Other, Personal, Other, My son is working in the pharma company TEVA as an engineer. I do not have any kind ofrelationship with TEVA TEVA;Non-Financial Interests, Personal, Leadership Role, Former President of Spanish Medical Oncology SocietyMember of the Spanish National Health Advisory Board SEOM;Non-Financial Interests, Personal, Leadership Role, Member of the Scientific Committee of the Spanish Against Cancer Research Foundation (aecc) and also Borad member AECC;Non-Financial Interests, Personal, Leadership Role, IASLC Women in Tho acic Oncology Working Group Member IASLC. All other authors have declared no conflicts of interest. Copyright © 2022