Clinical Study of HMPL-653 in Treatment of Advanced Malignant Solid Tumors and TGCT

Advanced Malignant Solid Tumors Clinical Trial

Official title:

A Multicenter, Open-label, Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-653 in Treatment of Patients With Advanced Malignant Solid Tumors and Tenosynovial Giant Cell Tumor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05277454
• Other study ID #: 2021-653-00CH1
• Status: Recruiting
• Phase: Phase 1
• Start date: January 18, 2022
• Est. completion date: April 14, 2025

Study information

• Verified date: January 2022
• Source: Hutchison Medipharma Limited
• Contact: Cindy Hua
• Phone: +86 21 2067 3221
• Email: cindyh[@]hutch-med.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the safety and tolerability of HMPL-653 in patients with advanced solid tumors who have failure of standard of care or can not tolerate standard of care or those with TGCT, and to determine the maximum tolerated dose (MTD) and/or the recommended phase II clinical study dose (RP2D) of HMPL-653 in patients with advanced solid tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 113
• Est. completion date: April 14, 2025
• Est. primary completion date: June 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Able to understand and willing to sign the ICF.

2. Aged 18 to 75 years.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. Life expectancy at least 12 weeks.

5. Adequate bone marrow, liver and kidney function.

Exclusion Criteria:

1. Toxicity associated with previous antitumor therapy not recovered to =CTCAE grade 1;

2. Previous treatment with anti-CSF1R therapy and have progressive disease;

3. Receiving approved systematic antitumor therapy or in the treatment period of other interventional clinical study within 4 weeks prior to the first dose.

4. Patients with central nervous system (CNS) malignant tumor or malignant solid tumor with known CNS metastasis;

5. Pregnant or lactating women.

Related Conditions & MeSH terms

• Advanced Malignant Solid Tumors
• Neoplasms

Intervention

Drug:
• HMPL-653
Dose-escalation Stage: Several dose levels will be evaluated for HMPL-653. The participants will receive oral HMPL-653 single-dose evaluation and oral HMPL-653 QD continuously treatment in a therapeutic cycle of 28 days until reaching the criteria for the end of treatment. Dose-expansion Stage: The participants will receive HMPL-653 treatment (RP2D)until reaching the criteria for the end of treatment.

Locations

Country	Name	City	State
China	Jilin Provincial Cancer Hospital	Chang chun
China	Harbin Medical University Cancer Hospital	Harbin
China	Linyi Cancer Hospital	Linyi
China	Henan Cancer Hospital	Zhengzhou
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of Dose-Limiting Toxicities(DLTs)	To evaluate the safety and tolerability of HMPL-653 for dose escalation period	up to 33 days
Primary	Maximum tolerated dose (MTD)	The Maximum tolerated dose of HMPL-653	up to 12 months
Primary	Recommended phase II dose (RP2D)	Recommended phase II dose of HMPL-653	up to 12 months
Secondary	Pharmacokinetic-Cmax	Peak concentration of Pharmacokinetic	up to 9 weeks
Secondary	Pharmacokinetic-Tmax	Time to peak concentration of Pharmacokinetic	up to 9 weeks
Secondary	Pharmacokinetic-Ctrough	Trough concentration of Pharmacokinetic	up to 9 weeks
Secondary	Pharmacokinetic-t1/2	Terminal elimination half-life of Pharmacokinetic	up to 9 weeks
Secondary	Pharmacokinetic-AUC0-t	Area under the plasma concentration-time curve of Pharmacokinetic	up to 9 weeks
Secondary	Pharmacokinetic-AUC0-8	Area under the plasma concentration-time curve of Pharmacokinetic	From first dose up to C3D1, estimated up to 9 weeks
Secondary	Pharmacokinetic-AUC0-t	Area under the plasma concentration-time curve of Pharmacokinetic	up to 9 weeks
Secondary	Pharmacokinetic-CL/F	Apparent clearance of Pharmacokinetic	up to 9 weeks
Secondary	Pharmacokinetic-Vz/F	Apparent volume of distribution in the terminal phase of Pharmacokinetic	up to 9 weeks
Secondary	Pharmacokinetic-AR	AUC-based accumulation coefficient of Pharmacokinetic	up to 9 weeks
Secondary	Objective response rate (ORR)	The incidence of confirmed complete response or partial response.	12 months
Secondary	Progression-free survival (PFS)	The time from the first dose of study treatment to PD or death for any reason, whichever comes first.	12 months
Secondary	Disease control rate (DCR)	The proportion of patients with confirmed CR or PR or stable disease (SD) as the best response, and the duration of SD needs to be =6 weeks.	12 months
Secondary	Time to response (TTR)	The time from the first dose of HMPL-653 to the first objective response.	12 months
Secondary	Duration of response (DoR)	The time from the first appearance of confirmed CR or PR to PD or death for any reason (whichever comes first), in the patients with objective response.	12 months
Secondary	Overall survival (OS)	The time from the first dose of study treatment to death for any reason.	24 months