LBA4 - 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)

Background

CAN is a monoclonal antibody that inhibits proinflammatory IL-1β–driven pathways that may play a role in tumor growth in early-stage NSCLC. Preclinical data suggest targeting IL-1β could decrease inflammation and immunosuppression in the tumor microenvironment (TME).

Methods

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 2:2:1 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.

Results

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). Table: LBA4

Biomarkers at screening (SCR) and surgery (SUR)

NS: p>0.05 *p≤ 0.05 **p≤ 0.01 ^aWilcoxon paired two sided ^bCD163 is a TAM biomarker ^cFOXP3 is a Treg biomarker

Conclusions

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-1β 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

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; Financial 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 Interests, 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 of relationship 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 Thoracic Oncology Working Group Member: IASLC. All other authors have declared no conflicts of interest.