Study of Anlotinib Plus Chemotherapy as the First-line Treatment in Patients With Advanced NSCLC

A Phase I/II Study of Anlotinib Combined With Platinum-based Chemotherapy as the First-line Treatment of Patients With Locally Advanced or Advanced Non-Small Cell Lung Cancer

Non-small cell lung cancer has the highest morbidity and mortality in China，and platinum-based chemotherapy is the standard first-line treatment for the wild-type NSCLC,however the overall survival still less than one year.Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR2、VEGFR3、PDGFRβ and c-Kit, which has strong effect of anti-angiogenesis.This study is aim to evaluate the efficacy and safety of the combination regimen of anlotinib plus platinum-based chemotherapy as first-line treatment for NSCLC.

Inclusion Criteria:

• Age：18~70 years;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 -2
• Subjects with histologically or cytologically confirmed locally advanced or advanced NSCLC
• EGFR\ALK\ROS1 wildtype or unknown,or patients with EGFR\ALK\ROS1 mutations but refuse to receive corresponding inhibitors' treatment
• No indications for radiation therapy
• Previously chemotherapy naive or postoperative adjuvant chemotherapy ended more than 1 year
• Subjects with at least one measurable lesion as defined by RECIST (version 1.1),which is confirmed by computed tomography (CT) scan or MRI

Exclusion Criteria:

• Small Cell Lung Cancer
• central lung squamous carcinoma along with cavum, or non-small cell lung cancer along with hemoptysis (>50ml/day)
• Within 30 days before enrollment, the patient had used any chemotherapy drugs in the previous treatment regimen or clinical study; Or, within 14 days before the first administration of the study therapy, the patient has used any targeted anticancer drugs in the previous treatment regimen or clinical study; Or stop other experimental drugs or cancer drugs for less than five half-life of the drug
• Previous use of anti-angiogenic drugs (such as anlotinib, apatinib, bevacizumab, endostar, etc.)
• have got non remissive toxic reactions derived from previous therapies, which is over level 1 in CTC AE (4.0), alopecia NOT included
• Spinal cord compression or symptomatic and untreated brain metastases (asymptomatic, stable, no need for steroid treatment for 4 weeks before study start)
• with kinds of factors which affect oral medicine (e.g. failing to swallow, gastrointestinal tract getting resected, chronic diarrhea and ileus)
• Previous histories include: interstitial pneumonia, drug-induced interstitial pneumonia, radiation pneumonia requiring steroid treatment, and clinically proven active interstitial pneumonia
• get arterial/venous thrombosis within 6 months, such as cerebrovascular accidents (including temporary ischemic stoke), prevenous thrombosis, and pulmonary embolism
• Have suffered from hemorrhagic disease or coagulation dysfunction
• diagnosed with disease which will severely endanger the security of patients or influence the completion of this research