1587TiPCANOPY phase III program: Three studies evaluating canakinumab in patients with non-small cell lung cancer (NSCLC)

• Published in: Annals of oncology Vol. 30; no. Supplement_5
• Main Authors: Paz-Ares, L, Garon, E B, Ardizzoni, A, Barlesi, F, Cho, B C, de Castro Junior, G, De Marchi, P, Felip, E, Goto, Y, Greystoke, A, Lu, S, Lim, D W-T, Papadimitrakopoulou, V A, Reck, M, Solomon, B J, Spigel, D, Tan, D S W, Thomas, M, Yang, J C-H, Johnson, B
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.10.2019
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdz260.109

Abstract Background The presence of inflammatory mediators in the tumor microenvironment may have pro or antitumorigenic effects. The cytokine interleukin-1β (IL-1β) affects multiple aspects of the tumor microenvironment promoting carcinogenesis, tumor invasiveness, and immunosuppression. Canakinumab is a human monoclonal antibody with high affinity and specificity for IL-1β. Results of the phase III Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) have shown that IL-1β inhibition with canakinumab was associated with reduced lung cancer incidence and mortality, providing a rationale to investigate the possible therapeutic role of canakinumab in lung cancer. Trial design Details of the three phase III trials designed in parallel to evaluate canakinumab in NSCLC are provided in the table below Table:1587TiP Overview of CANOPY programCANOPY-A (NCT03447769)CANOPY-1 (NCT03631199)CANOPY-2 (NCT03626545)Study designProspective, multicenter, randomized, double-blind, controlledSub-study: NSCLC patients (pts) who are candidates for complete resection surgery will be asked to participate in a biomarker sub-study to understand how resection surgery may impact hsCRP, other cytokines, and additional biomarker levels in bloodTwo parts: part 1 (open-label, safety run-in) and part 2 (randomized, placebo-controlled)Population*Stages IIA–IIIA and IIIB (T > 5 cm N2), completely resected, any histologyStage IIIB/IIIC–IV, squamous or nonsquamous, treatment naïve, ECOG PS ≤ 1, no EGFR sensitizing mutations nor ALK rearrangementsStage IIIB–IV, squamous or nonsquamous, previously treated with PD-L1 inhibitors and CTx, ECOG PS ≤ 1, no EGFR sensitizing mutations nor ALK rearrangementsEstimated enrollment1500 ptsPart 1: ≈27 pts (3 cohorts of ≈9 pts each, based on different platinum-chemotherapy (CTx) Part 2: 600 ptsPart 1: ≈9 pts Part 2: 226 ptsStratificationStage, histology, and geographic regionPD-L1 status, geographic region, and histologyNumber of prior lines of therapy and histologyTreatment arms and randomization ratio1:1 to canakinumab or placeboPart 1: •Cohort A (nonsquamous): canakinumab + pembrolizumab + carboplatin + pemetrexed •Cohort B (nonsquamous): canakinumab + pembrolizumab + cisplatin + pemetrexed •Cohort C (squamous or nonsquamous): canakinumab + pembrolizumab + carboplatin + paclitaxel Part 2: 1:1 to Canakinumab or placebo + platinum-CTx + pembrolizumabPart 1: canakinumab 200 mg s.c. + docetaxel 75mg/m2 i.v. on Day 1 of each 21-day cycle. Part 2: 1:1 to canakinumab or placebo + docetaxelTreatment schemeCanakinumab 200 mg Q3W SC18 cycles of treatment4 cycles of induction (canakinumab or placebo + CTx + pembrolizumab) followed by maintenance (canakinumab or placebo + pembrolizumab ± pemetrexed) until progressive disease (PD)†Treated until Progressive Disease (PD) as per investigator assessment by RECIST v1.1Primary endpointDisease-free survivalPart 1: Determination of recommended phase III regimen of canakinumab in combination with pembrolizumab plus platinum-based doublet CTx Part 2: Progression-free survival and overall survivalPart 1: Determination of recommended phase III regimen of canakinumab in combination with docetaxel Part 2: Overall survivalSecondary endpointsOverall survival, lung cancer specific survival, safety, patient reported outcomes, pharmacokinetics and immunogenicityIncludes overall response rate, disease control rate, time to response, duration of response, pharmacokinetics, safety, patient reported outcomes, and immunogenicityIncludes progression-free survival, overall response rate, disease control rate, time to response, duration of response, safety, patient reported outcomes, pharmacokinetics immunogenicity and time to ECOG performance status deterioration*stages as per AJCC/UICC v.8†For patients who continuing pembrolizumab ± canakinumab/matching placebo treatment beyond RECIST v1.1 PD as per investigator, tumor assessments will be done until immune-confirmed PD (iCPD) as per iRECIST per investigator or discontinuation of pembrolizumab ± canakinumab/matching placebo treatment, whichever occurs first.. Clinical trial identification NCT03447769, NCT03631199, NCT03626545. Editorial acknowledgement Aarti Kamaraj, Novartis Healthcare Pvt Ltd, Hyderabad, India. Legal entity responsible for the study Novartis Pharmaceuticals. Funding Novartis Pharmaceuticals. Disclosure L. Paz-Ares: Honoraria (self): Roche, Lilly, Novartis, Pfizer, MSD, BMS, Merck, Amgem, PharmaMar, Takeda Oncology, Sanofi, AstraZeneca, Boehringer Ing; Leadership role: Genomica; Travel / Accommodation / Expenses: Roche, Lilly, Novartis, Pfizer, MSD, BMS, Merck, Takeda Oncology, Sanofi, AstraZeneca, Boehringer Ing; Full / Part-time employment: University Hospital Doce de Octubre/Associate Professor Complutense University Madrid, Medicine Department. E.B. Garon: Honoraria (self): Dracen, EMD Serono; Research grant / Funding (institution): AstraZeneca, BMS, Genentech, Eli Lilly, Merck, Novartis, Neon, Iovance, Mirati, Dynavax. A. Ardizzoni: Honoraria (self): Eli Lilly, BMS, Pfizer, MSD; Advisory / Consultancy: Roche, MSD; Research grant / Funding (institution): Celgene, BMS, Roche. F. Barlesi: Honoraria (self): AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eli Lilly Oncology, ; Honoraria (self): F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda; Research grant / Funding (institution): AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, MedImmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis; Non-remunerated activity/ies, Principal Investigator : AstraZeneca, BMS, Merck, Pierre Fabre and F. Hoffmann-La Roche, Ltd, sponsored trials (or ISR); Research grant / Funding (institution): Takeda. B.C. Cho: Honoraria (self): Novartis, AstraZeneca, Bayer, Mogam Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD; Advisory / Consultancy: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (self): Novartis, AstraZeneca, Bayer, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD; Shareholder / Stockholder / Stock options: TheraCanVac Inc; Licensing / Royalties: Champions Oncology. G. de Castro Junior: Honoraria (self): MSD, BMS, Roche, Bayer, Novartis, Boehringer Ingelheim, AstraZeneca, Pfizer; Advisory / Consultancy: AstraZeneca, MSD, BMS, Roche, Novartis, Boehringer Ingelheim, Pfizer, Bayer, Merck Serono, Yuhan; Speaker Bureau / Expert testimony: MSD, BMS, Novartis, AstraZeneca, Pfizer, Roche, Bayer, TEVA; Research grant / Funding (institution): MSD, BMS, Roche, Novartis, Boehringer Ingelheim, AstraZeneca, Pfizer, Merck Serono; Travel / Accommodation / Expenses: MSD, BMS, Roche, Bayer, Novartis, Boehringer Ingelheim, AstraZeneca, Pfizer. P. De Marchi: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche, Bayer, MSD, BMS, Pfizer, Astrazeneca; Travel / Accommodation / Expenses: Roche, Msd, Bms, Astrazeneca . E. Felip: Advisory / Consultancy: AbbVie, AstraZeneca, Blue Print Medicines, Boehringer Ingelheim, Celgene, Eli Lilly, Guardant Health, Janssen, Medscape, Merck Kgaa, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Touchtime; Speaker Bureau / Expert Testimony: AbbVie, AstraZeneca, Boehringer Ingelheim, Celgene, Eli Lilly, Merck Kgaa, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Touchtime; Research Grant / Funding (Institution): Fundación Merck Salud, Grant For Ocnology Innovation; Officer / Board of Directors: Iaslc Board of Directors Member . Y. Goto: Advisory / Consultancy: Eli Lilly, Chugai, Taiho Pharmaceutical, Boehringer Ingelheim,Pfizer, Novartis, AstraZeneca, Glaxo Smith Kline, MSD, Guardant Health; Speaker Bureau / Expert testimony: AstraZeneca, Eli Lilly, Chugai, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, Bristol-Myers Squibb, Pfizer, MSD, Shionogi Pharma, Novartis; Research grant / Funding (institution): AbbVie, Eli Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb, Ono Pharmaceutical, Dai-ichi Sankyo, Pfizer, Novartis, Kyorin. A. Greystoke: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Novartis, Pfizer, Tesaro and Roche; Travel / Accommodation / Expenses: Takeda, Boehringer Ingelheim, MSD, Novartis, and Roche . S. Lu: Advisory / Consultancy, Research grant / Funding (self): AstraZeneca, BoehringerIngelheim, Hutchison and Roche; Speaker Bureau / Expert testimony: AstraZeneca, Hutchison Roche MediPharma, Simcere . D.W. Lim: Advisory / Consultancy: MSD, Novartis, AstraZeneca, Boerhinger-Ingelheim; Honoraria (self): MSD, Novartis, Boerhinger-Ingelheim. V.A. Papadimitrakopoulou: Advisory / Consultancy: Nektar Therapeutics, AstraZeneca, Arrys Therapeutics, Merck, LOXO Oncology, Araxes Pharma, F Hoffmann-La Roche, Janssen Research Foundation, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, Novartis, Takeda, AbbVie, TRM Oncology, Tesaro, Exelixis, Gritsto; Speaker Bureau / Expert testimony, speaker fees/non-speaker bureau: F Hoffmann-La Roche ; Research grant / Funding (institution): σ Eli Lilly, Novartis, Merck, AstraZeneca, F Hoffmann-La Roche, Nektar Therapeutics, Janssen, Bristol-Myers Squibb, Checkmate, Incyte . M. Reck: Honoraria (self), Advisory / Consultancy: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, Merck, MSD, Novartis, Roche, Pfizer. B.J. Solomon: Honoraria (self), Advisory / Consultancy: AstraZeneca, Roche/Genentech, Pfizer, Novartis, Merck, Bristol-Myers Squibb, Loxo Oncology. D. Spigel: Full / Part-time employment: Centennial Medical Center; Advisory / Consultancy: Genentech/Roche, Novartis, Celgene, Bristol-Myers Squibb, AstraZeneca, Pfizer, Boehringer Ing