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

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignant Mesothelioma
• Intervention / Treatment: Drug: HMPL-453

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wenjuan Ding; Phone Number: +8602120671806 +8602120671806; Email: Wenjuand@hmplglobal.com
• Study Contact Backup: Name: Chen Yu; Email: Cheny@hmplglobal.com

Study Locations

• China
  • Shanghai, China, 21000
    • Recruiting
    • Shanghai Chest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HMPL-453	Drug: HMPL-453; HMPL-453 tablet

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited
• Investigators: Principal Investigator: Shun Lu, Prof., Shanghai Chest Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2019
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): March 17, 2023

Study Registration Dates

• First Submitted: January 17, 2020
• First Submitted That Met QC Criteria: February 27, 2020
• First Posted (Actual): February 28, 2020

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 12, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant
• Other Study ID Numbers: 2019-453-00CH1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No