This is a multicenter, open label, Phase I/IIB study investigating the efficacy and safety of treatment with dacomitinib plus anlotinib as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) 21-L858R mutations. This study comprises two parts: 1. A dose escalation Phase I study to determine the recommended phase II dose. 2. a multi-center, open label, randomized controlled, Phase IIB study.

Inclusion Criteria:

1. ≥18 years of age and ≤75 years;
2. Provision of a voluntarily given, personally signed and dated, written informed consent document;
3. Histologically documented, unresectable, inoperable, locally advanced, recurrent or metastatic stage IIIB or IV non-small cell lung cancer (NSCLC);
4. 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;
5. At least one measurable disease by RECIST criteria version 1.1;
6. Patients with controlled or stable brain metastases;
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, and life expectancy of at least 3 months;
8. No prior treatment with systemic therapy for advanced NSCLC, including TCM treatments;
9. Able to comply with required protocol procedures and able to receive oral medications;
10. 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；

Exclusion Criteria:

1. Small cell lung cancer (including mixed small cell and non-small cell lung cancer) and squamous cell carcinoma with cavitation;
2. Patients with concurrent EGFR T790M mutation or unknown mutation status or other mutation types;
3. Diagnosis of any other malignancy during the last 5 years, or with other malignancies at present;
4. Patients with pre-existing meningeal metastases;
5. Patients who have concurrent other malignant tumors;
6. Any history of hemoptysis, hematochezia, bloody sputum;
7. Tumor invasion or adjacent major vessels;
8. 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;
9. 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;
10. Any astrointestinal disorders resulting in inability to take medications orally, or requiring intravenous (IV) nutrition, or previous surgery impair drug absorption;
11. Pregnant or lactating females;
12. Patients allergic to any pharmaceutical ingredient.