E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
stages AJCC v.8 IB-IIIA non-small cell lung cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
resectable non-small cell lung cancer (NSCLC) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the MPR rate (≤10% of residual viable tumor cells) at the time of surgery in evaluable subjects treated with canakinumab alone and in combination with pembrolizumab |
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E.2.2 | Secondary objectives of the trial |
1. To assess the prevalence and incidence of IG (ADA) of canakinumab and pembrolizumab 2. To assess ORR in randomized subjects treated with canakinumab or pembrolizumab as monotherapy or in combination 3. To assess PK of canakinumab and pembrolizumab as monotherapy and in combination 4. To assess surgical feasibility rate in each treatment arm based on randomized subjects 5. To assess the rate of MPR at the time of surgery in (a)evaluable subjects in pembrolizumab monotherapy arm, (b)evaluable subjects based on local review in each treatment arm, (c)randomized subjects based on both central and local review in each treatment arm and (d)to estimate the difference in MPR and posterior probability of the difference in MPR≥10% between canakinumab + pembrolizumab combination and pembrolizumab alone 6. To evaluate safety and tolerability of canakinumab and pembrolizumab as monotherapy or in combination 7. To assess the relationship between key blood or tissue based biomarkers and MPR |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed NSCLC stage IB-IIIA (per American Joint Committee on Cancer (AJCC) 8th edition), deemed suitable for primary resection by treating surgeon, except for N2 and T4 tumors. 2. Subject must be eligible for surgery and with a planned surgical resection in approximately 4-6 weeks (from the first dose of study treatment). 3. A mandatory newly obtained tissue biopsy is required for study enrollment. An archival biopsy is also acceptable if obtained up to 6 months before first day of study treatment and if the subject did not go through antineoplastic systemic therapies between biopsy collection date and beginning of study treatment. 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 5. Other protocol-defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
1. Subjects with unresectable or metastatic disease. All subjects should have brain imgaing (either Magnetic Resonance Imaging [MRI] brain or Computed Tomography [CT] brain with contrast) prior to enrollment to exclude brain metastasis. 2. History of severe hypersensitivity reactions to monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction. 3. Presence or history of a malignant disease that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type. Subjects who received prior systemic therapy (including chemotherapy, other anti-cancer therapies and any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) in the past 3 years before screening. 4. Other protocol-defined exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
MPR rate based on central review |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy analysis will be performed after all subjects have had surgical resection or have discontinued study treatment earlier due to any reason. |
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E.5.2 | Secondary end point(s) |
1. ADA prevalence at baseline and ADA incidence on-treatment 2. Overall response rate based on local investigator assessment per RECIST 1.1 3. Concentrations of canakinumab, pembrolizumab 4. Surgical feasibility rate 5. (a) MPR based on central review (b) MPR based on local review (c) MPR based on both central and local review (d) Difference in MPR rate based on central review 6. Type, frequency and severity of AEs (Common Terminology Criteria for Adverse Events [CTCAE] v5.0), vital signs and laboratory abnormalities 7. MPR based on the levels of biomarkers (PD-L1, CD8, hs-CRP, hs-IL-6) assessed at baseline and on treatment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoint analyses will be performed at the same time as the primary endpoint analysis (after all subjects have had surgical resection or have discontinued study treatment earlier due to any reason). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Canada |
France |
Germany |
Greece |
Hong Kong |
Hungary |
Japan |
Netherlands |
Russian Federation |
Spain |
Taiwan |
Turkey |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
When the last subject finishes their last safety follow-up visit at 130 days after last administration of study treatment and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator or, in the event of an early study termination decision, the date of that decision (each subject will be required to complete the study in its entirety and thereafter no further study treatment will be made available to them) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 16 |