Canakinumab for the Prevention of Lung Cancer, the Can-Prevent-Lung Trial

Inclusion Criteria

• The participant (or legally authorized representative if applicable) provides written informed consent for the trial
• Participants are eligible to be included in the study if one of the following criteria applies: * Patients with no history of lung cancer, who have persistent IPNs (on two computed tomography [CT] scans at least 3 months apart with no evidence of shrinkage or regression) detected by low dose computed tomography [LDCT]-guided lung cancer screening or imaging studies for other reasons (incidentalomas) with 10-30% cancer probability by Brock University cancer prediction equation as following * Patients with no history of lung cancer, who have persistent IPNs (on two CT scans at least 3 months apart with no evidence of shrinkage or regression) detected by LDCT-guided lung cancer screening or imaging studies for other reasons (incidentalomas) with > 30% cancer probability by Brock University cancer prediction equation as following, but biopsy showed no clear evidence of malignancy * Patients with history of stage I-III non-small cell lung cancer (NSCLC), who have completed treatment with curative intent, who have persistent IPNs (on two CT scans at least 3 months apart with no evidence of shrinkage or regression) with 5-30% cancer probability by Brock University cancer prediction equation as following * Patients with history of stage I-III NSCLC, who have completed treatment with curative intent, who have persistent IPNs (on two CT scans at least 3 months apart with no evidence of shrinkage or regression) with > 30% cancer probability by Brock University cancer prediction equation, but biopsy showed no clear evidence of malignancy
• Male/female participants who are at least 18 years of age on the day of signing informed consent
• A male participant must agree to use a contraception during the treatment period plus an additional 6months (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP) OR * A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 6 months after study treatments with risk of genotoxicity after the last dose of study treatment
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the start of study treatment
• Absolute neutrophil count (ANC) >= 1500/uL (collected within 10 days prior to the start of study treatment)
• Platelets >= 100 000/uL (collected within 10 days prior to the start of study treatment)
• Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (collected within 10 days prior to the start of study treatment) * Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• Creatinine =< 1.5 x upper limit or normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (collected within 10 days prior to the start of study treatment) * Creatinine clearance (CrCl) should be calculated per institutional standard
• Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (collected within 10 days prior to the start of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x ULN (collected within 10 days prior to the start of study treatment)

Exclusion Criteria

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
• Has received prior therapy with an anti-IL1beta
• Has a known additional malignancy that is progressing or has required active treatment within the past year. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
• Has an active infection requiring systemic therapy
• Known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (positive or indeterminate central laboratory results)
• 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 canakinumab treatment (unless otherwise required by health authorities or Institutional Review Board (IRB) in which case curative treatment must be completed prior to screening)
• Subjects with suspected or proven immunocompromised state or infections, including: * Known history of testing positive for human immunodeficiency virus (HIV) infections * 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 ** Note: Subjects with localized condition unlikely to lead to a systemic infection (e.g. chronic nail fungal infection) are eligible * Allogeneic bone marrow or solid organ transplant * Those requiring systemic or local treatment with any immune modulating agent in doses with systemic effects e.g.: ** Prednisone > 20 mg (or equivalent) oral or intravenous daily for > 14 days at the time of canakinumab treatment; ** Prednisone > 5 mg and =< 20 mg (or equivalent) daily for > 30 days at the time of canakinumab treatment; ** Equivalent dose of methotrexate > 15 mg weekly at the time of canakinumab treatment *** Note: Daily glucocorticoid-replacement for conditions such as adrenal or pituitary insufficiency is allowed. Topical, inhaled or local steroid use in doses that are not considered to cause systemic effects are permitted. Steroids for pre-medication related to chemotherapy as per local standard of care are permitted
• History of hypersensitivity to canakinumab or drugs of a similar class
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through 6 months after the last dose of trial treatment
• Is receiving the following therapies during the screening and treatment phases (including retreatment for post-complete response relapse) of this trial: antineoplastic systemic chemotherapy or biological therapy, immunotherapy not specified by this protocol, chemotherapy not specified by this protocol, investigational agents other than canakinumab
• Has received live vaccines within 30 days prior to first dose of study treatment and while participating in the study. Examples of live vaccines include but are not limited to: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guerin (BCG) and typhoid vaccine. (Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however intranasal influenza vaccines (eg FluMist are live attenuated vaccines are not allowed)
• Has active tuberculosis (TB) after confirmed laboratory and imaging scans. If negative, this can be considered as latent TB and should be treated with prophylactic antibiotics before initiating canakinumab treatment