A Study of WXFL10030390 in Patients With Advanced Solid Tumors or Lymphoma

A Phase Ⅰ Study of PI3K/mTOR Dual Inhibitor WXFL10030390 to Evaluate the Safety, Tolerability and Pharmacokinetics in Patients With Advanced Solid Tumors or Lymphoma

WXFL10030390 (WX390) is a novel oral small molecular that inhibits phosphoinositide-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) and has demonstrated potent inhibitory effects on multiple human tumor xenografts. The first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of WX390 at single dose and multiple doses.

This study will be an open-lable, phase Ⅰ study and will evaluate the safety and pharmacokinetics of WX390 after a single administration followed by a 28-day continuous course of therapy; evaluate the safety and preliminary efficacy in an open-lable administration of WX390 at the MTD.

Inclusion Criteria:

• ≥18 and ≤75 years of age
• Histological or cytological confirmed advanced solid tumor or lymphoma, standard regimen failed or no standard regimen available
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Life expectancy of more than 3 months
• At least one measurable lesion according to RECIST 1.1 or Lugano 2014
• Adequate organic function: Absolute neutrophil count (ANC) ≥2.0×109/L，PLT≥100×109/L，Hb≥9g/L hepatic function:TBIL≤1.5×upper limit of normal (ULN)，Alanine aminotransferase (ALT) ≤2.5×ULN，aspartate aminotransferase (AST) ≤2.5×ULN; renal function:Cr≤1.5×ULN and>50ml/min; coagulation function: APTT≤1.5 ×ULN，PT≤1.5 ×ULN, INR≤1.5 ×ULN; GLU<7mmol/L and HbA1C<7%; TG≤1.5×ULN，CHOL≤1.5×ULN
• Subjects who have the fertility should agree to use reliable contraceptive methods during this study and subsequently at least 12 weeks after the last administration; for female subjects, the blood pregnancy test should be negative within 7 days prior to the enrollment
• Signed and dated informed consent

Exclusion Criteria:

• Anti-cancer therapy within 4 weeks prior to the initiation of investigational treatment
• Surgery within 4 weeks prior to the initiation of study treatment
• Use of strong inducers or inhibitors of CYP3A4 within 1 weeks before the first dose of study treatment. See Appendix 5 for a list of such medications
• Received corticosteroids treatment or other immunodepressant within 2 weeks before the first dose of study treatment
• Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1 (except for alopecia)
• Patients with clinical symptomatic brain metastases, spinal compression, meningitis carcinomatosa or other evidence that shows uncontrolled brain or spinal metastases
• Previous treatment with PI3K/mTOR inhibitors
• Patients who once or being suffer Interstitial lung disease
• Evidence of ongoing or active infection
• History of human immunodeficiency virus (HIV) infection
• History of hepatitis B or C infection
• Clinically significant cardiovascular disease, including but not limited to acute coronary syndrome, congestive heart-failure, cerebral stroke within 6 months prior to enrollment, New York Heart Association Class ≥II cardiac functional grading or left ventricular ejection fraction (LVEF) < 50%
• Inability to take medication orally
• Severe gastrointestinal disease leading to diarrhea
• Diabetics receiving insulin treatment
• Patients with active autoimmune disease (including systemic lupus erythematosus, rheumatoid arthritis, nodular vasculitis)
• Abuse of alcohol or drugs
• People with cognitive and psychological abnormality or with low compliance
• Pregnant or lactating women
• Researchers believe that subjects may not be able to complete the study or may not be able to comply with the requirements of this study