HMPL-453 in Advanced Malignant Mesothelioma

A Phase II, Single Arm, Multicenter and Open Labelstudy Evaluating the Efficacy, Safety and Pharmacokinetics of HMPL-453 in Patient With Advanced Malignant Mesothelioma

This is a phase II, single arm, multicenter and open-label study to evaluate the efficacy, safety and pharmacokinetic of HMPL-453 in patient with advanced Malignant Mesothelioma

Histologically confirmed patients with advanced malignant mesothelioma that who was failure of the first -line systemic therapy

Inclusion Criteria:

• 1.Signed written informed consent;
• 2.18 years of age or older;
• 3.Histologically diagnosed malignant mesothelioma (including pleura, peritoneum, pericardium, and testicular tendon sheath origin, cell type epithelioid, sarcoma-like, or mixed type), and cannot be cured radically;
• 4.Received one to three regimen of prior systemic therapy and then experienced documented radiographic progression or intolerable toxicity;
• 5.Patients agreed to provide tumor tissue for FGF/FGFR testing;
• 6.Measurable disease by RECIST version 1.1 criteria;
• 7.ECOG performance status ≤ 2.;

Exclusion Criteria:

• 1.Previous treatment with any FGFR inhibitor;

• 2.Received systemic anti-cancer therapy within 3 weeks of the first dose of HMPL-453;

• 3.Major surgery within 4 weeks of the first dose of HMPL-453;

• 4.Use of a strong inducer or inhibitor of cytochrome P450 3A4 (CYP3A4) within 1 week of the first dose of HMPL-453;

• 5.Inadequate conditions as indicated by the following laboratory values:

  • Absolute neutrophil count (ANC)<1.5 x 109/L
  • Hemoglobin < 80 g/L
  • Platelet count <80 x 109/L

• 6.Any of the following conditions of liver and kidney insufficiency:

  • Total bilirubin > 1.5 x ULN
  • AST and ALT > 2.5 x ULN (> 5 x ULN for patients with liver metastases)
  • Creatinine clearance of < 50 mL/min as estimated by the Cockcroft-Gault equation

• 7.International normalized ratio (INR) >1.5 or activated partial thromboplastin time (aPTT) >1.5 x ULN;

• 8.Clinical significant liver disease;

• 9.Known human immunodeficiency virus (HIV) infection

• 10.Previous history of retinal detachment;

• 11.Unable to swallow the study drug.