Safety, Tolerability and Pharmacokinetics of Simmiparib in Patients With Malignant Advanced Solid Tumor

Inclusion Criteria:

1. Patients confirmed with advanced solid tumor based on pathology and/or cytology, considered unresponsive or poorly responsive to standard therapies, no curative therapies or can't tolerate standard therapies;
2. Patients must have measurable disease in accordance with RECIST criteria v. 1.1, at least one lesion that can be accurately measured in CT and MRI at least one dimension ( longest diameter≥10mm; if lymph node, short diameter≥15mm );
3. Age≥18 and ≤75 years, both men and women, no history of drug abuse and alcohol;
4. Life expectancy≥ 3 months and can be followed for safety and efficiency
5. Received no prior anti-tumor therapies at least within past 4 weeks and no other adjuvant anti-tumor regimen(including steroids mediations )
6. Have recovered to≤ common terminology criteria of adverse events (CTC-AE) 1 from toxicities of prior therapy
7. Not participated in any clinical trials within 28 days;
8. Not have received treatment of poly-ADP ribose polymerase (PARP) inhibitor;
9. No serious abnormal hematopoiesis function, has adequate cardiac, pulmonic, hepatic and renal function. Blood routine and blood biochemical examination within 2 weeks before enrollment : White blood cell (WBC) ≥4000/mm3, Absolute neutrophil count (ANC) ≥1,500/mm3, Platelets ≥100,000/mm3, Coagulation function ≤ 1.5 times upper limit of normal (ULN), serum creatinine ≤ 1.5 times ULN, Total bilirubin ≤ 1.5 times ULN, Patients without liver metastasis, Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)≤ 2.5 times ULN; Patients with liver metastasis, Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/≤ 2.5 times ULN, NYHAclass≤Ⅱand Left ventricular ejection fraction ( LVEF)\>50%;
10. Virology test: negative HbsAg, HCV, HIV and syphilis
11. Eastern Cooperative Oncology Group(ECOG) performance status ≤2;
12. No history of other malignant tumors, except cervical carcinoma in situ, basal skin cancer or squamous-cell carcinoma that have been cured; No other serious illnesses that are in conflict with this study and significant heart disease and psychosis;
13. Ability to understand and a willingness to sign a written informed consent; Obtaining consent before any operation

Exclusion Criteria:

1. Patients with serious medical disease, including, severe cardiopathy, vascular disease, uncontrolled diabetes, uncontrolled hypertension, severe infection , or psychosis, etc.;
2. Patients with primary brain lesion or metastases lesion;
3. Female patient who is pregnant, breast feeding or unwilling to contraception;
4. Patient who received or is receiving any other investigational agents within 4 weeks prior to treatment;
5. Patients, with poor compliance, or based on the opinion of the investigator, should not be enrolled into this study;
6. has not recovered to grade 1 or better from any adverse events related to previous therapy.
7. Neurotoxicity observed in previous antineoplastic therapy has not recovered to grade 1 or below.