Safety, Efficacy, and Tumor Immune Microenvironment Changes With Neoadjuvant Chemotherapy and Cemiplimab With or Without Alirocumab in Stage 1B-3A Non-Small Cell Lung Cancer: TOP 2301
In this open-label, two-arm, randomized phase 2 clinical trial, patients with clinical stage 1B-3A non-small cell lung cancer (NSCLC) will receive neoadjuvant chemotherapy and cemiplimab every 3 weeks for 3 cycles with or without alirocumab every 4 weeks prior to surgery. Eligible patients will be randomized with equal allocation to two treatment groups. Permuted block randomization algorithm will be used for treatment assignment with stratification factors: stage (1B, 2A, 2B, 3A), and performance status (0 vs. 1). The study hypothesis is that the addition of alirocumab to neoadjuvant chemoimmunotherapy will make tumor cells more immunogenic to cytotoxic T cells, resulting in an increase in complete pathologic responses in surgically resected tumor.
• Age ≥ 18 years.
• Histological/cytological diagnosis of non-small cell lung cancer (NSCLC). Patient is eligible to enroll in the study based on clinical suspicion of NSCLC but are required to have a histological diagnosis of NSCLC in order to be eligible to receive treatment on study.
• Clinical stage IB, IIA/IIB, or III (N0-2) amenable to surgical resection.
• Primary tumor size of ≥ 3 cm (for all clinical stages to insure adequate tumor for correlative studies).
• Agrees to research blood collections for study.
• Deemed a surgical candidate.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• No prior chemotherapy, radiation therapy or biologic/targeted therapy for current diagnosis of lung cancer.
• Measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
⁃ No active invasive malignancy in the past 2 years other than non-melanoma skin cancer. Cancers that are in-situ are not considered invasive.
⁃ Signed written informed consent including Health Insurance Portability and Accountability Act (HIPAA) according to institutional guidelines.
⁃ Sexually active males and females of reproductive potential must agree to use an appropriate contraceptive method during the study and for 120 days following the last dose of study drug.
⁃ Females of childbearing potential must test negative for pregnancy within 48 hours prior to any initial study procedure based on a serum pregnancy test. (If subject uses appropriate contraceptive methods from the time of the initial serum pregnancy test, then the subsequent pregnancy test can be done within 72 hours prior to start of study treatment. If appropriate contraceptive measures are not begun immediately with the first serum pregnancy test, then subsequent serum pregnancy tests must be done within 48 hours prior to the start of study treatment.)
⁃ Adequate organ function defined as:
∙ Absolute neutrophil count (ANC) ≥ 1500 per uL
‣ Platelets ≥ 100,000 per uL
‣ Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or growth factor dependency (within 7 days of assessment)
‣ Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 60 mL/min for subject with creatinine levels \> 1.5 x ULN
‣ Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN
‣ Aspartate aminotransferase (AST) \[serum glutamic-oxaloacetic transaminase (SGOT)\] and alanine aminotransferase (ALT) \[glutamic-pyruvic transaminase (SGPT)\]≤ 2.5 x ULN
‣ Albumin ≥ 2.5 mg/dL
‣ International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy and within therapeutic range of intended use of anticoagulants
‣ Activated Partial Thromboplastin Time (aPTT) ≤1.5 x ULN unless subject is receiving anticoagulant therapy and within therapeutic range of intended use of anticoagulants