First-line Treatment With Dacomitinib Plus Anlotinib for Patients With Advanced NSCLC With EGFR 21L858R Mutations

Prior treatment

• Patients who have concurrent other malignant tumors;
• Any astrointestinal disorders resulting in inability to take medications orally, or requiring intravenous (IV) nutrition, or previous surgery impair drug absorption;

Other illness

• Small cell lung cancer (including mixed small cell and non-small cell lung cancer) and squamous cell carcinoma with cavitation;
• Diagnosis of any other malignancy during the last 5 years, or with other malignancies at present;
• Any history of hemoptysis, hematochezia, bloody sputum;
• Patients with uncontrolled or significant systematic disease, including: active infection, thyroid dysfunction, uncontrolled hypertension, unstable angina pectoris, congestive heart failure, or myocardial infarction within 6 months, or severe arrhythmia requiring medication;
• Patients allergic to any pharmaceutical ingredient.

Lab values

• Patients with concurrent EGFR T790M mutation or unknown mutation status or other mutation types;
• A history of other diseases, or metabolic dysfunction, or physical examination or laboratory results suggestive of a disease or condition that precludes the use of an investigational drug, or may affect the interpretation of the study results, or expose the patient to a high risk of treatment complications;

Other

• Patients with pre-existing meningeal metastases;
• Tumor invasion or adjacent major vessels;
• Pregnant or lactating females;

• ≥18 years of age and ≤75 years;
• Provision of a voluntarily given, personally signed and dated, written informed consent document;
• Histologically documented, unresectable, inoperable, locally advanced, recurrent or metastatic stage IIIB or IV non-small cell lung cancer (NSCLC);
• It is acceptable for subjects with the presence of EGFR activating mutation (exon 19 deletion and the L858R mutation in exon 21) to be included in this Phase I study; Only subjects with the L858R mutation in exon 21 to be included in this Phase IIb;
• At least one measurable disease by RECIST criteria version 1.1;
• Patients with controlled or stable brain metastases;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, and life expectancy of at least 3 months;
• No prior treatment with systemic therapy for advanced NSCLC, including TCM treatments;
• Able to comply with required protocol procedures and able to receive oral medications;
• Adequate organ function, including:
  • (1) Adequate bone marrow function Hemoglobin≥90g/L, absolute neutrophil count (ANC) should be ≥ 1.5x109/L, platelets should be ≥ 80x109/L; (2) Adequate liver function Total bilirubin ≤ 1.5 x upper normal limit (ULN), Aspartate Aminotransferase (AST) (SGOT) ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases), Alanine Aminotransferase (ALT) (SGPT) ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases), Creatinine≤ 1.5 x upper normal limit (ULN), or ≥ 60 mL/min; (3) Cardiac function: LVEF≥50% assessed by Doppler ultrasound；