A Phase I Study of TQB3616 on Tolerance and Pharmacokinetics

Inclusion criteria

• ≥18 years old
• Patients definitely diagnosed by pathology and/or cytology as advanced breast cancer with ER+、Her2-,who failed with standard endocrine therapy.
• ECOG PS:0-1,Survival is expected to be greater than 3 months
• Main organs function is normal or must meet the following criteria(within past 14 days) 1) hemoglobin≥90g/L; neutrophils≥1.5 x109/L; Platelets≥100 x109/L 2)Albumin≥29g/L; total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase(AST) and alanine transaminase(ALT)≤2.5 ULN, and ≤ 5 x ULN with hepatic metastasis;serum creatinine ≤1.5 xULN，creatinine clearance >60ml/min; Triglyceride≤3.0mmol/L, cholesterol≤7.75mmol/L

3)Doppler ultrasound evaluation: Left ventricular ejection fraction(LVEF)≥50% 5.Patients should be voluntary and sign the informed consent before taking part in the study

Exclusion criteria

• Patients with malignant tumors, except for Cured cutaneous basal cell carcinoma and cervical carcinoma in situ
• Prior treatment with chemotherapy with cytotoxic drugs within 4 weeks, mitomycin C or nirtosocarbamide within 8 weeks
• Prior treatment with any anti-cancer therapy including hormone therapy radioimmunotherapy, molecular targeted therapy, immunotherapy or other biological therapy with 2 weeks
• Patients treated with other CDK4/6 inhibitors;
• Patients with brain metastasis, spinal cord compression, cancerous meningitis, CT or MRI examination reminds patients with cerebral or soft meningeal diseases in the screening phase;
• Previous history of stem cell or bowe marrow transplant;
• A variety of factors that affect oral medication (such as inability to swallow, gastrointestinal resection, intestinal obstruction, etc.)
• Patients with non-healing wounds or fractures, except for bone metastatics with pathologic frature
• Previous history of uncontrolled cardiovascular disease including: a) Grade 3 or higher congestive heart failure (NYHA Classification);b)unstable angina pectoris or newly developped angina pectoris within 3months before the trial; c) Myocardial in farction or stroke occured within 6 months prior to intiation of trial; d) Arrhythmias requiring antiarrhythmic treatment(beta-blocker or digoxin is permitted)
• Patients who need to take CYP3A4 inhibitors or inducers from the screening period;
• Patients with drug abuse history or unable to get rid of drugs or Patients with mental disorders
• Patients with the urine protein≥2+, total ammount of 24 hours urinary protein determination>1.0 grams;
• Patients with hyperactive/venous thrombosis events within 6 months,such as cerebrovascular accidents (including temporary ischemic attack), deep venous thrombosis and pulmonary embolism
• Patients with active hepatitis b or c infection
• Patients with immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disease, or organ transplant history;
• Patients allergic to TQB3616 or any adjuvant in the capsule
• Patients who took part in other trials within 4 weeks;
• Patients with concomitant diseases which could seriously endanger themselves or those who won't complete the study according to investigators;