Neoadjuvant Icotinib With Chemotherapy for Epidermal Growth Factor Receptor(EGFR)-Mutated Resectable Lung Adenocarcinoma

Neoadjuvant Icotinib With Chemotherapy for Resectable Stage II-IIIB N2 EGFR Mutation-positive Lung Adenocarcinoma: A Phase II Study

Icotinib is a first-generation inhibitor of EGFR-tyrosine kinase inhibitor in patients with non-small-cell lung cancer (NSCLC). Here we will evaluate neoadjuvant Icotinib with chemotherapy prior to surgery, in patients with resectable stage II-IIIB N2 EGFR mutation-positive NSCLC. The primary endpoint is centrally assessed major pathological response at the time of resection. Secondary endpoints include pathological complete response, objective response rate, R0 resection rate at the time of resection, disease-free survival, and overall survival. Safety and tolerability will also be assessed.

Key Inclusion Criteria:

• Written informed consent

• Male or female, aged ≥18 years and ≤75 years

• Histologically or cytologically documented lung adenocarcinoma with completely resectable disease (Stage II-IIIB N2, according to the 8th edition of the IASLC Staging Manual in Thoracic Oncology)

• Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by an MDT evaluation

• A tumor which harbors either Ex19del or L858R EGFR-TKI-sensitizing mutations, either alone

• ECOG PS 0/1 at enrollment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing

• Adequate organ and marrow function as defined by:

  • Hemoglobin: ≥9.0 g/dL
  • Absolute neutrophil count: ≥1.5 × 109/l
  • Platelet count: ≥100 × 109/l
  • Serum bilirubin: ≤1.5 ULN
  • ALT and AST: ≤2.5 × ULN
  • Creatinine clearance: ≥60 ml/min

• Life expectancy of 6 months prior to randomization

Exclusion Criteria:

• Prior treatment with systemic anti-cancer treatment for NSCLC, EGFR-TKI treatment or pre-operative radiotherapy
• EGFR-TKI-sensitizing mutations with T790M
• Mixed small cell and non-small-cell lung cancer histology
• T4 tumors infiltrating the aorta, esophagus and/or heart
• Bulky N2 disease
• Candidates for segmentectomies or wedge resections only
• Medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment or any evidence of clinically active ILD
• Severe or uncontrolled systemic diseases/active infections, history of allogeneic organ transplantation, history of primary immunodeficiency, history of another primary malignancy