Étude évaluant l’efficacité et la sécurité d’emploi du canakinumab par rapport au placebo en tant que traitement adjuvant après résection d’un cancer du poumon

Product Name: canakinumab
Product Code: ACZ885
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2
Current Sponsor code: ACZ885
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: canakinumab
Product Code: ACZ885
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2
Current Sponsor code: ACZ885
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Gender:
Female: yes
Male: yes

Inclusion criteria:
Subjects eligible for inclusion in this study have to meet all of the
following criteria at the time of screening:
1.1.Written informed consent must be obtained prior to any screening
procedures.
2.Age = 18 years
3a. Completely resected (R0) NSCLC AJCC/UICC v. 8 stage IIA-IIIA and
IIIB (T>5cm, N2 disease only).
The maximum number of days allowed from surgery to randomization is:
? 70 days if subjects were treated with surgery, but did not receive
chemotherapy or radiation.
? 182 days if subjects were treated with surgery and chemotherapy,
but no radiation.
? 259 days if subjects were treated with surgery, chemotherapy and
radiation
7a. Subjects must have recovered from all toxicities related to prior
systemic therapy to grade = 1 (CTCAE v 5.0). Exception to this criterion:
subjects with any grade of alopecia, neuropathy (grade =2), and
subjects meeting the laboratory specifications described in inclusion 8.
8. Subjects must have adequate organ function including the following
laboratory values at the screening visit:
? Absolute neutrophil count (ANC) = 1.5 x 109/L
? Platelets = 100 x 109/L
? Hemoglobin (Hgb) > 9 g/dL
? Creatinine clearance greater than 45 ml/min using Cockcroft-Gault
formula
? Total bilirubin = 1.5 x ULN
? Aspartate transaminase (AST) = 3 x ULN
? Alanine transaminase (ALT) = 3 x ULN
9. ECOG performance status (PS) of 0 or 1.
10. Willing and able to comply with scheduled visits, treatment plan and
laboratory tests.

Inclusion criteria applicable for sub-study (CACZ885T2301A)
1. Written informed consent to sub-study must be obtained prior to any
collections.
2. Age = 18 years
3. Subjects with NSCLC Stage IIA-IIIA, IIIB (T>5cm, N2 disease only) who are
candidates for
complete resection surgery.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 825
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 675

Exclusion criteria:
1. Subjects with unresectable or metastatic disease, positive
microscopic margins on the pathology report, and/or gross disease
remaining at the time of surgery.
2. Subjects who received any neoadjuvant treatment.
3a. Presence or history of a malignant disease, other than the resected
NSCLC, that has been diagnosed and/or required therapy within the past
3 years.
4a. History of clinically significant interstitial lung disease (= grade 2).
5a. History or current diagnosis of cardiac disease, including any of the
following:
? recent myocardial infarction or coronary artery bypass graft (CABG)
surgery within last 6 months,
? uncontrolled congestive heart failure,
? unstable angina (within last 6 months),
? clinically significant (symptomatic) cardiac arrhythmias
6a.Thoracic radiotherapy to lung fields = 4 weeks prior to starting cycle
1 day 1 or subjects who have not recovered from radiotherapy-related
toxicities.
7. Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic)
within 4 weeks prior to randomization or who have not recovered from
side effects of such procedure. Video-assisted thoracic surgery (VATS)
and mediastinoscopy will not be counted as major surgery and subjects
can be enrolled in the study =1 week after the procedure.
8. Uncontrolled diabetes as defined by the investigator.
9. Known active or recurrent hepatic disorder including cirrhosis,
hepatitis B and C (positive or indeterminate central laboratory results).
10a. Subjects must be evaluated for tuberculosis as per local treatment guidelines or clinical practice. Subjects with active tuberculosis are not
eligible. In subjects without active tuberculosis, if the results of the
evaluation require treatment per local guidelines, then the treatment
should be initiated before randomization (unless otherwise required by
Health Authorities or IRB in which case curative treatment must be
completed prior to screening).
11a. Subjects with suspected or proven immunocompromised state or
infections, including:
a. Known history of testing positive for Human Immunodeficiency Virus
(HIV) infections.
b. Those with any other medical condition such as active infection,
treated or untreated, which in the opinion of the investigator places the
subject at an unacceptable risk for participation in immunomodulatory
therapy.
c. Allogeneic bone marrow or solid organ transplant
d. Those requiring systemic or local treatment with any immune
modulating agent in doses with systemic effects e.g.:
i. Prednisone >20 mg (or equivalent) oral or intravenous daily for >14
days;
ii. Prednisone > 5 mg and = 20 mg (or equivalent) daily for > 30 days;
iii. Equivalent dose of methotrexate >15 mg weekly.
12a. Live or attenuated vaccination within 3 months prior to first dose of
study drug (e.g. MMR, Yellow Fever, Rotavirus, Smallpox, etc.).
13. Prior treatment with canakinumab or drugs of a similar mechanism
of action (IL-1? inhibitor).
14. History of hypersensitivity to canakinumab or drugs of a similar
class.
15. Subjects who have received an investigational drug or device within
30 days prior to first dose of study drug or those who are expected to
participate in any other investigational drug or device during the conduct
of the study.
16. Subjects who received any biologic drugs targeting the immune
system at any time.
17. Any medical condition resulting in a life expectancy of less than 5
years, other than the risk for recurrent lung