Neoadjuvant Toripalimab for Clinically Stage II-IIIB Resectable Non-small Cell Lung Cancer with EGFR Mutation and PD-L1 Positive Expression

Inclusion criteria

• Men and women aged ≥ 18 years old.
• Baseline tumor tissues have to be obtained through biopsy (percutaneous or transbronchial) or surgery at study center.
• Histologically confirmed diagnosis of primary non-small lung cancer on non-squamous histology.
• Pre-treatment stage as clinical II-IIIB (AJCC/UICC 8th Edition) (stage IIIB excludes N3 disease); curative resectability has to be explicitly verified by the experienced surgical investigator.
• Confirmation by the central laboratory that the tumor harbors EGFR mutations either sensitive mutations, uncommon mutations or complex mutations.
• Have a PD-L1 tumor proportion score (TPS) ≥ 1% determined by IHC at the central laboratory. In order to balance patients with high PD-L1 expression (≥50%) and low PD-L1 expression (1-49%), we planned to enroll PD-L1 high and low patients at a ratio of 1:1.
• Have not received prior systemic treatment for NSCLC.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Expected survival ≥ 3 months.
• Adequate blood and organ function.

Exclusion criteria

• Patients with histologically confirmed squamous cell carcinoma, combined small cell carcinoma and large cell carcinoma.
• Molecular testing confirmed ALK translocation.
• Treatment with prior systemic cancer therapy for the current lung cancer at any time (chemotherapy, radiotherapy, target therapy, ablation, and any other local or systemic therapy).
• Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colorectal, endometrial, cervical, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.
• Any active or history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications. Subjects with vitiligo, type I diabetes mellitus, resolved childhood asthma/atopy, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.
• Subjects with a history of interstitial lung disease, pneumonitis, or poorly controlled lung disease (including pulmonary fibrosis, acute lung diseases).
• Severe chronic or active infections that require systemic antimicrobial, antifungal, or antiviral treatment, including tuberculosis infections.
• Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL \[2500 copies/mL\] should be excluded.
• Has known active hepatitis C virus (HCV). Active HCV is defined by positive tests for HCV Ab and quantitative HCV RNA.
• Known positive history or positive test for Human Immunodeficiency Virus (HIV).
• The investigator believes that there is a high risk of bleeding (such as esophageal varices with bleeding risk, local active ulcer lesions) or active hemoptysis.
• History of allergy to study drug components.
• Pregnant and lactating women are excluded.
• Fertile men or their female partners (women of childbearing potential, WOCBP) who are not willing to use contraception.
• Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information.
• The investigator believes that there are factors that can increase medication risk or confuse outcome judgment.