Neoadjuvant Chemo-Immunotherapy and Surgical Resection in Locally Advanced Non-small Cell Lung Cancer With N3 Lymph Node Involvement

NCT06449313 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00007668
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

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.

Conditions

Non-small Cell Lung Cancer Stage III

Keywords

non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (pCR) rate

  Pathologic complete response (pCR): 0% viable tumor in primary tumor and resected lymph nodes.

  12 weeks

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  1 year

• Rate of R0 Resection

  12 weeks

• Major pathologic response (MPR) rate

  12 weeks

• Disease-free Survival (DFS)

  5 years

• Overall Survival (OS)

  5 years

Study Arms (1)

Cemiplimab plus chemotherapy

EXPERIMENTAL

cemiplimab given with standard of care chemotherapy for 4 treatments/cycles before surgery and then every 3 weeks for 1 year after surgery.

Drug: Cemiplimab-Rwlc

Interventions

Cemiplimab-Rwlc DRUG

350 mg every 3 weeks, intravenously, on day 1 of a 21 day cycle for 4 cycles, then every 3 weeks after surgery for 1 year.

Also known as: Libtayo

Cemiplimab plus chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided all of following conditions are met: Disease is well controlled at baseline and requires only low-potency topical corticosteroids; No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency oral corticosteroids within the previous 12 months
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• Known active tuberculosis.
• Known history of poorly controlled HIV. Patients living with HIV are allowed to enroll if: (1) they are clinically stable on appropriate highly active anti-retroviral therapy (HAART) with undetectable HIV viral load and CD4 count \>350 and (2) the HAART regimen poses no unacceptable interactions with the prescribed anti-cancer therapies.
• Known history of poorly controlled hepatitis B or hepatitis C
• Patients with known hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus (HBV) DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards and must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.

Sponsors & Collaborators

• Georgetown University: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (3)

Lombardi Comprehensive Cancer Center, Georgetown University

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Washington University School of Medicine-Sitemen Cancer Center

St Louis, Missouri, 63110, United States

RECRUITING

UVA Comprehensive Cancer Center

Charlottesville, Virginia, 22908, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Joshua Reuss, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joshua Reuss, MD

CONTACT

202-444-2223; Joshua.E.Reuss@gunet.georgetown.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 10, 2024
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): September 1, 2032
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)