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

JYA0101

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.

2018-10-25

2020-07-25

2020-07-25

Completed

Early phase I

82

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 82, 'type': 'ACTUAL'}}

2023-04-18