Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.

Inclusion Criteria:

• Subjects must have treatment-naive unresectable stage III NSCLC according to theAJCC 8th edition staging;

• Squamous or non-squamous NSCLC histology;

• Subjects should have a rare mutation based on NGS, including mutations of EGFRexon20ins, ROS1 fusion, RET fusion, NTRK fusion, MET 14 exon, HER2, BRAF V600E, KRASG12C, and ALK fusion.

• Subjects should be without EGFR exon 19 deletions or exon 21 L858R activatingmutation;

• Male and female, aged 18-75 years;

• Blood and specimens before and after treatment must be provided;

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;

• Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, andPlatelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintainor exceed this level);

• Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN),Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN;

• Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min;

• Female subjects should not be pregnant or breast-feeding;

• Written informed consent provided. Being willing and able to comply with the visits,treatment plan, laboratory examinations and other study procedures scheduled in thestudy.

Exclusion Criteria:

• Not unresectable stage III disease according to the investigator;

• Subjects with known EGFR sensitive mutations;

• Previous treatment with systemic antitumor therapy for NSCLC;

• Eye inflammation or eye infection not fully treated or conditions predisposing thesubject to this.

• History of another malignancy in the last 5 years with the exception of thefollowing: other malignancies cured by surgery alone and having a continuousdisease-free interval of 5 years are permitted. Cured basal cell carcinoma of theskin and cured in situ carcinoma of the uterine cervix are permitted.

• Evidence of clinically active interstitial lung disease;

• Known history of testing positive for human immunodeficiency virus (HIV) or knownacquired immunodeficiency syndrome (AIDS);

• Inability to comply with protocol or study procedures;

• Any unstable systemic disease (including active infection, active tuberculosisuncontrolled hypertension, unstable angina, congestive heart failure, myocardialinfarction within the previous year, serious cardiac arrhythmia requiringmedication, hepatic, renal, or metabolic disease);

• A serious concomitant systemic disorder that, in the opinion of the investigator,would compromise the patient's ability to complete the study and may confuse thestudy results;

• Women who are pregnant or nursing.

• Ingredients mixed with small cell lung cancer patients.