first-line treatment with dacomitinib plus anlotinib for patients with advanced nsclc with egfr 21l858r mutations

Conditions: Non-Small Cell Lung Cancer (NSCLC)

Summary: 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.


Eligibility criteria:
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.