Nadunolimab for the Treatment of High-Risk Lung Nodules for Current or Former Smokers

Inclusion Criteria

• Patients must be current or former tobacco smokers (> 20 pack years)
• Patients must have multi-focal part-solid nodules (≥ 2 lesions, at least one with solid component < 9mm) with evidence of progression on at least one annual follow-up CT scan
• Patients must not meet criteria for surgical intervention at the time of enrollment
• Patient must be willing and able to provide blood samples (12 green-top tubes, roughly 100mL) at the five time points indicated in the Study Calendar
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) 0-1. The exception will be patients carrying long term disability (such as cerebral palsy) where the disability is not acute nor progressive, and unlikely to significantly affect their response to therapy. This must be documented in screening clinic visit note by investigator
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 1 month and 6 months following completion of therapy, for woman and men, respectively. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 24 consecutive months
• Ability to understand and the willingness to sign a written informed consent
• Absolute neutrophil count (ANC) ≥ 1,500 /mcL
• Platelets ≥ 100,000 /mcL
• Hemoglobin ≥ 9 g/dL
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) ≥ 60 mL/min GFR for patient with creatinine levels > 1.5 X institutional ULN * Creatinine clearance should be calculated per institutional standard. * If laboratory criteria are not met due to what the investigator determines to be a biologic cause (e.g. Gilbert’s syndrome causing elevated bilirubin or excessive muscle mass affecting creatinine) or drug-related cause (e.g. elevating in transaminases due to highly active antiretroviral therapy [HAART] therapy, elevated international normalization ratio [INR] due to anticoagulation) then the specific lab values will not be used to exclude patient from this trial. This determination will be made by principal investigator (PI)
• Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN * If laboratory criteria are not met due to what the investigator determines to be a biologic cause (e.g. Gilbert’s syndrome causing elevated bilirubin or excessive muscle mass affecting creatinine) or drug-related cause (e.g. elevating in transaminases due to HAART therapy, elevated INR due to anticoagulation) then the specific lab values will not be used to exclude patient from this trial. This determination will be made by PI
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X ULN * If laboratory criteria are not met due to what the investigator determines to be a biologic cause (e.g. Gilbert’s syndrome causing elevated bilirubin or excessive muscle mass affecting creatinine) or drug-related cause (e.g. elevating in transaminases due to HAART therapy, elevated INR due to anticoagulation) then the specific lab values will not be used to exclude patient from this trial. This determination will be made by PI
• Albumin ≥ 2.5 mg/dL * If laboratory criteria are not met due to what the investigator determines to be a biologic cause (e.g. Gilbert’s syndrome causing elevated bilirubin or excessive muscle mass affecting creatinine) or drug-related cause (e.g. elevating in transaminases due to HAART therapy, elevated INR due to anticoagulation) then the specific lab values will not be used to exclude patient from this trial. This determination will be made by PI

Exclusion Criteria

• Any pulmonary nodule with a solid component > 8mm
• Patients may not be receiving any other investigational agents at the time of enrollment
• Uncontrolled intercurrent illness prior to starting therapy including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (≤ 10 days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. * Exception: Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded
• Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). * Exception: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient’s participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
• Known HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with < 200 CD4+ T cells/microliter in the peripheral blood. HIV testing is not required for patients with no known history of HIV
• Has known Hepatitis B or active Hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected). Hepatitis B virus (HBV) and HCV testing is not required for patients with no known history of these viruses
• History of allogeneic hematopoietic cell transplantation or solid organ transplantation
• Receipt of a live vaccine, etanercept, or tumor necrosis factor-alpha inhibitors within 30 days of planned start of study drug
• Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps) Principal investigator believes that for one or multiple reasons the patient will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the patient