HMPL-453 in Advanced Malignant Mesothelioma

Phase 2

• Conditions: Advanced Malignant Mesothelioma
• Interventions: Drug: HMPL-453

• Registration Number: NCT04290325
• Lead Sponsor: Hutchison Medipharma Limited

Brief Summary

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

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

Study Timeline

• Study Start: 2019-12-30
• Study First Submitted: 2020-01-17
• Study First Submitted QC: 2020-02-27
• Study First Posted: 2020-02-28
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-12
• Last Update Posted: 2020-06-16
• Primary Completion: 2022-11-30
• Study Completion: 2023-03-17

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 27

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HMPL-453	HMPL-453	HMPL-453

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	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	Evaluating ORR of HMPL-453 in patient with advanced malignant mesothelioma

Secondary Outcome Measures

Name	Time	Method
Disease control rate (DCR)	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	Evaluating DCR of HMPL-453 in patient with advanced malignant mesothelioma
12 weeks DCR	measured on 12 weeks	Evaluating 12 weeks DCR of HMPL-453 in patient with advanced malignant mesothelioma
Time to Response (TTR)	measured on 4 weeks	Evaluating TTR of HMPL-453 in patient who achieved partial response or complete response according to RECIST 1.1 or mRECIST 1.1
Duration of response (DoR)	measured on 30 weeks	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.
Overall survival (OS)	measured on 60weeks	Evaluating OS of HMPL-453 in patient with advanced malignant mesothelioma
Maximum plasma concentration (Cmax) of HMPL-453	measured on Cycle 1 day 15 and day 16	Evaluating Cmax of Continuous dosing of HMPL-453 in patient with advanced malignant
12 weeks PFS	measured on 12 weeks	Evaluating 12 weeks PFS rate of HMPL-453 in patient with advanced malignant mesothelioma
Progression free survival (PFS)	measured on 20 weeks	Evaluating PFS of HMPL-453 in patient with advanced malignant mesothelioma.
Adverse Event (AE) of HMPL-453 monitoring	Measured from the first dose to within 30 days after the end of treatment.	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.
The time to Cmax (Tmax) of HMPL-453	measured on Cycle 1 day 15 and day 16	Evaluating Tmax of Continuous dosing of HMPL-453 in patient with advanced malignant
The area under the plasma concentration-time curve (AUC) of HMPL-453	measured on Cycle 1 day 15 and day 16	Evaluating AUC from 0 to the time of the last measurable concentration of HMPL-453 in patient with advanced malignant

Trial Locations

Locations (1)

Shanghai Chest Hospital; 🇨🇳 Shanghai, China