Abstract 5103
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 program
| CANOPY-A (NCT03447769) | CANOPY-1 (NCT03631199) | CANOPY-2 (NCT03626545) | |
|---|---|---|---|
| Study design | Prospective, multicenter, randomized, double-blind, controlled | ||
| Sub-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 blood | Two 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 histology | Stage IIIB/IIIC–IV, squamous or nonsquamous, treatment naïve, ECOG PS ≤ 1, no EGFR sensitizing mutations nor ALK rearrangements | Stage IIIB–IV, squamous or nonsquamous, previously treated with PD-L1 inhibitors and CTx, ECOG PS ≤ 1, no EGFR sensitizing mutations nor ALK rearrangements |
| Estimated enrollment | 1500 pts | Part 1: ≈27 pts (3 cohorts of ≈9 pts each, based on different platinum-chemotherapy (CTx) Part 2: 600 pts | Part 1: ≈9 pts Part 2: 226 pts |
| Stratification | Stage, histology, and geographic region | PD-L1 status, geographic region, and histology | Number of prior lines of therapy and histology |
| Treatment arms and randomization ratio | 1:1 to canakinumab or placebo | Part 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 + pembrolizumab | Part 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 + docetaxel |
| Treatment scheme | Canakinumab 200 mg Q3W SC | ||
| 18 cycles of treatment | 4 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 v1.1 | |
| Primary endpoint | Disease-free survival | Part 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 survival | Part 1: Determination of recommended phase III regimen of canakinumab in combination with docetaxel Part 2: Overall survival |
| Secondary endpoints | Overall survival, lung cancer specific survival, safety, patient reported outcomes, pharmacokinetics and immunogenicity | Includes overall response rate, disease control rate, time to response, duration of response, pharmacokinetics, safety, patient reported outcomes, and immunogenicity | Includes 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 Ingelheim, AbbVie, Foundation Medicine, GlaxoSmithKline, Lilly, Merck, Moderna Therapeutics, Nektar, Takeda, Amgen, TRM Oncology, Precision Oncology, Evelo Therapeu; Research grant / Funding (institution): Genentech/Roche, Novartis, Celgene, Bristol-Myers Squibb, Lilly, AstraZeneca, Pfizer, Boehringer Ingelheim, AbbVie, Merck, University of Texas Southwestern Medical Canter-Simmons Cancer Center, GlaxoSmithKline, G1 Therapeutics, Neon Therapeutics, Takeda,; Travel / Accommodation / Expenses: AstraZeneca, Boehringer Ingelheim, Celgene, Lilly, EMD Serono, BMS, Genentech, Genzyme, Intuitive Surgical, Merck, Pfizer, Purdue Pharma, Spectrum Pharmaceuticals, Sysmex. D.S.W. Tan: Honoraria (self): Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda ; Advisory / Consultancy: Novartis, Bayer, Boehringer Ingelheim, Celgene, ; Research grant / Funding (self): Novartis, AstraZeneca, GlaxoSmithKline, Bayer, Pfizer ; Travel / Accommodation / Expenses: Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche,Takeda . M. Thomas: Honoraria (self), Advisory / Consultancy: AbbVie, BMS, Boehringer, Celgene, Lilly, MSD, Novartis, Roche, Takeda; Speaker Bureau / Expert testimony: Lilly, MSD, Takeda; Research grant / Funding (self): AstraZeneca, BMS, Celgene, Roche; Travel / Accommodation / Expenses: BMS, Boehringer, MSD, Novartis. J.C. Yang: Advisory / Consultancy: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, Chugai Pharmaceutical, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceuticals, Daiichi-Sankyo, Hansoh Pharmaceuticals, Takeda Pharmaceuticals; Honoraria (self): Boehringer Ingelheim, Eli Lilly, Bayer, Roche, Chugai Pharmaceutical, MSD, Pfizer, Novartis, BMS, Ono Pharmaceuticals, , AstraZeneca; Advisory / Consultancy: Blueprint Medicines, AstraZeneca, G1 Therapeutics. B. Johnson: Research grant / Funding (institution): Novartis, Canon Medical Systems; Licensing / Royalties, post-marketing royalties for EGFR mutation testing as one of the inventors of the technology: Dana-Farber Cancer Institute.
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