The Study Of Andamertinib Plus Anlotinib In Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This study is a single arm study to access the anti-tumor efficacy and safety of Andamertinib plus Anlotinib in patients with locally advanced or metastatic non-small cell lung cancer previously treated with third-generation EGFR-TKI.

Inclusion Criteria: 1. Able to understand and voluntarily sign the written informed consent form. 2. Aged ≥ 18 years, male or female. 3. Non-small-cell lung cancer (NSCLC) confirmed histologically or cytologically, clinically diagnosed as unresectable and ineligible for curative concurrent chemoradiotherapy, including locally advanced (stage ⅢB/ⅢC), metastatic or recurrent (stage Ⅳ) NSCLC. 4. Harboring EGFR mutations (including exon19 deletions and exon21 L858R mutation), with documented disease progressed following only one prior line of third-generation EGFR-TKI therapy. 5. At least one measurable lesion per RECIST v1.1. Lesions previously irradiated cannot serve as target lesions unless definitive progression has occurred in the irradiated lesion. 6. Patients with asymptomatic brain metastases, or brain metastases whose symptoms have stabilized after treatment. 7. Laboratory values meeting all of the following criteria: (1) Hemoglobin ≥100g/L (female), ≥110g/L (male). (2) Absolute neutrophil count ≥1.5×10⁹/L. (3) Platelet count ≥100×10⁹/L. (4) Serum creatinine ≤115 μmol/L, or creatinine clearance (CrCl) ≥60mL/min (Cockcroft-Gault formula). (5) Total bilirubin ≤1.5×upper limit of normal (ULN). (6) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN; or ≤5×ULN for patients with liver metastases. (7) Albumin ≥30g/L. 8. ECOG PS 0-1. 9. Expected survival ≥3 months. 10. Males with reproductive potential and females of child-bearing potential must agree to use effective contraception from the time of informed consent signing until 3 months after the last study drug administration. For females of child-bearing potential, serum pregnancy test must be negative within 7 days prior to the first study drug dose. Women with surgical sterilization or post-menopausal status are exempted. Exclusion Criteria: 1. Diagnosis of other malignant diseases within 3 years prior to first study drug administration, except for radically treated basal cell carcinoma of the skin, squamous-cell carcinoma of the skin, and/or radically resected carcinoma in-situ. 2. Presence of any of the following genetic alterations: ALK fusion, ROS1 fusion, BRAF V600 mutation, NTRK fusion, MET exon14 skipping mutation, MET amplification, RET fusion, KRAS G12C mutation, HER2 mutation, NRG1 fusion. 3. Central squamous-cell carcinoma with high risk of massive hemoptysis. 4. Toxicities from prior anti-tumour therapy have not recovered to Grade≤1, except for alopecia, fatigue and other toxicities judged by the investigator to carry low safety risk. 5. Prior treatment with sunvozertinib. 6. Major surgery (e.g., intrathoracic, intra-abdominal or pelvic surgery) within 4 weeks before first study drug administration, or resection for brain metastases within 2 weeks, with incomplete recovery from surgical adverse effects. Thoracoscopic biopsy and mediastinoscopy are not considered major surgery; subjects may be enrolled ≥1week after such procedures. Thoracic/abdominal effusion drainage and needle biopsy are not regarded as surgery. 7. Severe or uncontrolled systemic diseases, including but not limited to: (1) Uncontrolled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg despite treatment; antihypertensive agents may be initiated or adjusted prior to screening). (2) Positive HIV antibody; or positive HCV antibody plus positive HCV-RNA; or positive HBsAg with HBV-DNA ≥500 IU/mL. Exception: subjects may be enrolled if HBV-DNA decreases to \< 500 IU/mL and remains so for ≥2 weeks under antiviral therapy during screening, and antiviral therapy must be continued throughout the study. Subjects who require antiviral therapy at screening or in the past must maintain antiviral therapy for the whole study period. (3) Active keratitis or ulcerative keratitis. (4) Active tuberculosis. (5) Active infection requiring systemic anti-infective therapy within 2 weeks prior to first study drug administration. (6) Other severe physical or psychiatric illnesses or laboratory abnormalities that, in the investigators opinion, make study drug inappropriate or compromise protocol compliance. 8\. Any of the following cardiac conditions: 1. Mean QTcF (QTc corrected by Fridericia formula) from three screening ECGs \>470 ms at rest. 2. Significant arrhythmias including ventricular arrhythmias, pharmacologically uncontrolled supraventricular/nodal arrhythmias and other uncontrolled cardiac arrhythmias (e.g., complete left bundle-branch block, grade III atrioventricular block, grade II atrioventricular block, PR interval \>250 msec). 3. Risk factors for QTc interval prolongation: e.g., severe hypokalaemia, congenital long-QT syndrome, concomitant use of QTc-prolonging drugs. 4. New York Heart Association (NYHA) congestive heart failure class ≥3; left ventricular ejection fraction (LVEF) \