BIOLUMA: Biomarkers for Nivolumab and Ipilimumab and Evaluation of the Combination in Lung Cancer

Inclusion Criteria

• •Note: Both cohorts are closed for enrollment
• •Cohort 1: Subjects with histologically or cytologically confirmed advanced non-squamous non-small cell lung cancer who present with stage IIIB or stage IV disease after failure of platinum-based first-line therapy. Subjects who received adjuvant/neoadjuvant therapy or definitive chemoradiation and develop recurrence or progression, with evidence of stage IIIB-IV disease within 6 months after completion of therapy, are eligible.
• •Cohort 2: Subjects in Cohort 2 have to undergo Prescreening to determine Tumor Mutation Burden. Only patients with high Tumor Mutation Burden are eligible.
• •Subjects with histologically or cytologically confirmed limited-stage or extensive-stage small cell lung cancer after failure of platinum-based first-line therapy.
• •Cohort 1 and Cohort 2:
• •Signed and dated written informed consent form must be obtained before the performance of any study-specific procedure
• •Male or female patients ≥ 18 years of age
• •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• •Subjects must be willing to undergo the baseline biopsie during screening, if medically feasible
• •Measurable disease by CT or MRI per RECIST 1.1 criteria.
• •Screening laboratory values must meet the following criteria and should be obtained within 28 days prior to registration: white blood cell count ≥ 2000/μL, Neutrophils ≥ 1500/μL, Platelets ≥ 100 x103/μL, Hemoglobin \> 9.0 g/dL, Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min, AST/ALT ≤ 3 x ULN for patients without liver metastasis, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5 x ULN for patients with liver metastasis, Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• •Prior chemotherapy must have been completed at least 4 weeks before study drug administration, and all AEs have either returned to baseline or stabilized.
• •Prior palliative radiotherapy must have been completed at least 14 days prior to study drug administration
• •Prior targeted therapy must have been completed at least 4 weeks prior to study drug administration
• •Cohort 2b: Subjects with CNS metastases are eligible. Radiation of CNS metastases at initiation of study drug treatment is allowed if the trial subject has target lesions outside of the brain.
• •Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception and must agree to use adequate method to avoid pregnancy for 5 month after the last dose of study drug.
• •Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of b-HCG) within 24 hours prior to the start of nivolumab.
• •Women must not be breastfeeding.
• •Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP must be willing to adhere to contraception for a period of 7 month post treatment completion.
• •Presence or history of any other primary malignancy other than NSCLC for Cohort 1 and SCLC for Cohort 2 within 5 years prior to enrolment into the trial, except for adequately treated basal or squamous cell carcinoma of the skin or any adequately treated in situ carcinoma.
• •Active, known or suspected autoimmune disease. Subjects are permitted to enrol if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• •Positive test for hepatitis B or hepatitis C indicating acute or chronic infection
• •Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• •Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first dose of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• •Note for Cohort 2b: higher doses of corticosteroids for patients receiving radiation therapy of brain metastases are allowed.
• •Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• •Prior systemic treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
• •Note: SCLC-Patients who where treated with a combination therapy of platinum-based chemotherapy together with anti-PD-1/PD-L1 treatment are eligible.
• •Prisoners or subjects who are involuntarily incarcerated.
• •Any other serious or uncontrolled medical disorder, active infections, physical exam findings, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject's ability to comply with the study requirements, substantially increase risk to the subject, or impact the interpretability or study results.
• •Allergies and Adverse Drug Reaction: History of allergy to study drug components and history of severe hypersensitivity reaction to any monoclonal antibody
• •Current treatment within another therapeutic clinical trial