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
Overview
- Phase
- Phase 2
- Intervention
- Cemiplimab-Rwlc
- Conditions
- Non-small Cell Lung Cancer Stage III
- Sponsor
- Georgetown University
- Enrollment
- 21
- Locations
- 5
- Primary Endpoint
- Pathologic complete response (pCR) rate
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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-
- •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
Exclusion Criteria
- •NSCLC with histology containing any of the following: large cell neuroendocrine carcinoma, small cell lung cancer.
- •Primary tumor not deemed appropriate for surgical resection as assessed by treating surgeon.
- •Tumor with direct invasion of: mediastinum, diaphragm, heart, great vessels, trachea, esophagus, vertebral body, or carina.
- •Any other tumor characteristic making it not suitable for resection as determined by treating surgeon.
- •Any prior systemic therapy for index lung cancer, including immunotherapy, chemotherapy.
- •History of malignancy requiring systemic therapy within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death as assessed and confirmed by the study PI. (Patients with a history of stage I NSCLC treated with resection or radiotherapy are eligible for inclusion.)
- •Active or history of clinically significant autoimmune disease that, in the opinion of the investigator, could compromise the health and safety of the patient if treated with anti-PD1 immunotherapy. Notable exceptions include:
- •Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone.
- •Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen.
- •Active or history of adrenal insufficiency on stable steroid regimen.
Arms & Interventions
Cemiplimab plus chemotherapy
cemiplimab given with standard of care chemotherapy for 4 treatments/cycles before surgery and then every 3 weeks for 1 year after surgery.
Intervention: Cemiplimab-Rwlc
Outcomes
Primary Outcomes
Pathologic complete response (pCR) rate
Time Frame: 12 weeks
Pathologic complete response (pCR): 0% viable tumor in primary tumor and resected lymph nodes.
Secondary Outcomes
- Objective Response Rate (ORR)(1 year)
- Overall Survival (OS)(5 years)
- Rate of R0 Resection(12 weeks)
- Major pathologic response (MPR) rate(12 weeks)
- Disease-free Survival (DFS)(5 years)