HMPL-453 in Advanced Malignant Mesothelioma

Study Overview
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Brief Summary
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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

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

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

Conditions
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Advanced Malignant Mesothelioma

Intervention / Treatment
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* Drug: HMPL-453


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HMPL-453<br>HMPL-453 | Drug: HMPL-453<br>* HMPL-453 tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Evaluating ORR of HMPL-453 in patient with advanced malignant mesothelioma | measured up to 6 months after the last subject has been enrolled or all subjects have finished their last PFS follow up, whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) | Evaluating DCR of HMPL-453 in patient with advanced malignant mesothelioma | measured up to 6 months after the last subject has been enrolled or all subjects have finished their last PFS follow up, whichever comes first | 
| 12 weeks DCR | Evaluating 12 weeks DCR of HMPL-453 in patient with advanced malignant mesothelioma | measured on 12 weeks | 
| Time to Response (TTR) | Evaluating TTR of HMPL-453 in patient who achieved partial response or complete response according to RECIST 1.1 or mRECIST 1.1 | measured on 4 weeks | 
| Duration of response (DoR) | Evaluating DoR of HMPL-453 in patient from subject first achieve a complete remission, or partial remission to patient PD, or death whichever comes first. | measured on 30 weeks | 
| 12 weeks PFS | Evaluating 12 weeks PFS rate of HMPL-453 in patient with advanced malignant mesothelioma | measured on 12 weeks | 
| Progression free survival (PFS) | Evaluating PFS of HMPL-453 in patient with advanced malignant mesothelioma. | measured on 20 weeks | 
| Overall survival (OS) | Evaluating OS of HMPL-453 in patient with advanced malignant mesothelioma | measured on 60weeks | 
| Adverse Event (AE) of HMPL-453 monitoring | The safety endpoints include adverse events (AEs) and serious adverse events (SAEs). Reporting of safety, extent of exposure, concomitant medications and discontinuation of study therapy will be based on all subjects who received at least 1 dose of treatment. The adverse events will be registered according to NCI CTCAE 5.0. | Measured from the first dose to within 30 days after the end of treatment. | 
| Maximum plasma concentration (Cmax) of HMPL-453 | Evaluating Cmax of Continuous dosing of HMPL-453 in patient with advanced malignant | measured on Cycle 1 day 15 and day 16 | 
| The time to Cmax (Tmax) of HMPL-453 | Evaluating Tmax of Continuous dosing of HMPL-453 in patient with advanced malignant | measured on Cycle 1 day 15 and day 16 | 
| The area under the plasma concentration-time curve (AUC) of HMPL-453 | Evaluating AUC from 0 to the time of the last measurable concentration of HMPL-453 in patient with advanced malignant | measured on Cycle 1 day 15 and day 16 |