A Phase 2 Single-Arm Study of Neoadjuvant Chemo-Immunotherapy and Surgical Resection in Locally Advance Non-Small Cell Lung Cancer (NSCLC) With N3 Lymph Node Involvement
The goal of this clinical trial is to learn about neoadjuvant cemiplimab with histology-specific chemotherapy followed by resection and adjuvant cemiplimab in stage 3 non-small cell lung cancer (NSCLC) with contralateral mediastinal or ipsilateral supraclavicular lymph node (N3) involvement.. The main question it aims to answer is whether patients with stage 3 NSCLC with involvement of lymph nodes can undergo surgery to remove the cancer after receiving treatment with chemotherapy + immunotherapy. Participants will receive FDA-approved chemotherapy called platinum-doublet chemotherapy together with an immunotherapy drug targeting the immune marker PD-1 called cemiplimab. Patients will receive a 3 drug combination for 4 total treatments given every 3 weeks before surgery. After surgery, patients will have the option to undergo radiation therapy if it is recommended by their treatment team. After this, they will receive cemiplimab every 3 weeks for one year.
• Age ≥ 18 years at time of signing the informed consent form (ICF).
• Histologically or cytologically confirmed stage 3 B/C Non-Small Cell Lung Cancer (NSCLC) as assessed per the 8th American Joint Committee on Cancer (AJCC) with pathologically-confirmed contralateral mediastinal or ipsilateral supraclavicular (N3) lymph node involvement.
• Primary tumor appropriate for resection with curative intent as assessed by the treating surgeon prior to study enrollment.
• Absence of major associated pathologies and co-morbidities that elevate surgery risk to a prohibitive level, as assessed by treating surgeon prior to study enrollment.
• Pulmonary function capacity capable of tolerating the lung resection proposed by the treating surgeon.
• EGFR, ALK, wild-type assessed via any CLIA-certified tissue testing platform. Documentation of EGFR and ALK status is not required for pure squamous NSCLC histology.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 21 days prior to initiation of study treatment:
∙ Absolute Neutrophil count (ANC) ≥ 1.0 x 10\^9/L (1000/uL) without granulocyte colony-stimulating factor support
‣ Platelet count ≥ 100 x 10\^9/L (100,000/uL) without transfusion
‣ Hemoglobin ≥ 90 g/L (9.0 g/dL) (Patients may be transfused to meet this criterion.)
‣ Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \</= 3 x upper limit of normal (ULN)
‣ Serum bilirubin \</= 2.0 x ULN with the following exception: Patients with known Gilbert disease: serum bilirubin \</= 3 x ULN
‣ Creatinine clearance ≥ 45 mL/min (calculated using the Cockcroft-Gault formula). If creatinine clearance determined by Cockcroft-Gault is \<45 mL/min, another appropriate validated formula or 24hr urine collection may be used in consultation with the study PI.
‣ For patients not receiving therapeutic anticoagulation: INR (international normalised ratio) and aPTT (activated partial thromboplastin time) \</= 1.5 x ULN. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen defined as clinical stability on unchanged dose of therapeutic anticoagulation for ≥14 days.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
• Women must remain abstinent or use highly effective contraceptive methods with a failure rate of \< 1% per year during the treatment period and for at least 4 months after the final dose of study treatment. Women must refrain from donating eggs during this same period.
• A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
• Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
⁃ For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
• With a female partner of childbearing potential who is not pregnant, or a female partner who is pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for 4 months after the final dose of study treatment. Men must refrain from donating sperm during this this same period.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.