Exploratory Study Evaluating the Potential of Immune Signature Profiling for Predicting Response in Patients With Resectable Stage II, IIIA and Select IIIB (T3N2 Only) Non-squamous Non-Small Cell Lung Cancer (NSCLC) to Neoadjuvant ATEZOLIZUMAB Plus Carboplatin/Nab Paclitaxel
Exploratory study evaluating the potential of immune signature profiling for predicting response in patients with resectable Stage II, IIIA and select IIIB (T3N2 only) non-squamous Non-Small Cell Lung Cancer (NSCLC) to neoadjuvant ATEZOLIZUMAB plus Carboplatin/nab Paclitaxel Atezolizumab is given as intravenous infusion at a fixed dose of 1200 mg, day 1 of each 21-day cycle (every 3 weeks) for 3 cycles during the neoadjuvant treatment phase, Carboplatin at an initial dose of AUC (area under curve) 5 mg/mL/min, intravenously day 1 of each 21-day cycle for 3 cycles during the neoadjuvant treatment Phase, and Nab-Paclitaxel (Abraxane) at 100 mg/m2, intravenously day 1, 8 and 15 of each 21-day cycle for 3 cycles during the neoadjuvant treatment phase. Surgery after the 3rd cycle Atezolizumab / Carboplatin / Nab-Paclitaxel is standard procedure.
• Informed consent, patients age ≥ 18-year-old including, signed and dated
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Histologically confirmed NSCLC of non-squamous histology, cStage II, IIIA or select IIIB (T3N2 only); for T-status ≤ T3 allowed; for N2 patients only IIIa1-3 Robinson classification allowed
• Deemed surgically resectable with curative intent by an attending thoracic surgeon after adequate staging including PET-CT (positron emission tomography)
• Adequate lung and cardiac function for intended lung resection according to German S3 regulation
• Radiologically measurable disease as defined by response evaluation criteria in solid tumors RECIST v1.1
• Sufficient availability of the tissue sample from primary tumor before start of neoadjuvant treatment
• Females of child-bearing potential must agree to use, and be able to comply with, effective contraception (\</=1% failure rate annually) without interruption, 28 days prior to starting therapy (including dose interruptions), and while on study medication or for a period of 120 days after the last dose of study medication
• Females must have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy.
• Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following treatment discontinuation, even if he has undergone a successful vasectomy.
• adequate renal, hepatic, and bone marrow function as defined below
‣ Absolute neutrophil count (ANC) \> 1500/μl
⁃ Platelet count ≥ 100000/μl
⁃ Hemoglobin ≥ 9 g/dl (can be post-transfusion)
⁃ International normalized ratio (INR) ≤ 1.4 in patients not receiving anticoagulation; for patients receiving respective anticoagulation an INR ≤3.0 allowed
⁃ Activated partial thromboplastin time (aPTT) ≤ 1.5 times upper limit of normal (ULN) in patients not receiving anticoagulation; for patients receiving respective anticoagulation a PTT ≤2.5 ULN allowed
⁃ Bilirubin \< 1.5 times ULN (for patients with known Gilbert disease Bilirubin ≤ 3 times ULN allowed)
⁃ ALT and AST \< 2.5 times ULN
⁃ Creatinine ≤ 1.5 ULN or calculated creatinine clearance \> 60 ml/min for subjects with creatinine levels \> 1.5 ULN; for patients meeting the criterion of creatinine ≤ 1.5 ULN also a calculated creatinine clearance of \> 30 ml/min is mandatory