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

Phase 1

Recruiting

• Conditions: Advanced Malignant Solid Tumors; TGCT
• Interventions: Drug: HMPL-653

• Registration Number: NCT05277454
• Lead Sponsor: Hutchison Medipharma Limited

Brief 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2022-01
• Study Start: 2022-01-18
• Study First Submitted: 2022-02-06
• Study First Submitted QC: 2022-03-11
• Last Update Submitted: 2022-03-11
• Study First Posted: 2022-03-14
• Last Update Posted: 2022-03-14
• Primary Completion: 2024-06-28
• Study Completion: 2025-04-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 113

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HMPL-653 open-label treatment arm	HMPL-653	Dose-escalation Stage: Participants will be treated with escalating doses of HMPL-653 to determine the MTD and RP2D. Dose-expansion Stage: Participants will be enrolled in the expansion stage to better characterize the safety, tolerability, PK variability, and preliminary efficacy of HMPL-653 in TGCT and specific advanced solid tumors.

Primary Outcome Measures

Name	Time	Method
Occurrence of Dose-Limiting Toxicities(DLTs)	up to 33 days	To evaluate the safety and tolerability of HMPL-653 for dose escalation period
Maximum tolerated dose (MTD)	up to 12 months	The Maximum tolerated dose of HMPL-653
Recommended phase II dose (RP2D)	up to 12 months	Recommended phase II dose of HMPL-653

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic-AR	up to 9 weeks	AUC-based accumulation coefficient of Pharmacokinetic
Pharmacokinetic-Cmax	up to 9 weeks	Peak concentration of Pharmacokinetic
Pharmacokinetic-Tmax	up to 9 weeks	Time to peak concentration of Pharmacokinetic
Pharmacokinetic-Ctrough	up to 9 weeks	Trough concentration of Pharmacokinetic
Pharmacokinetic-t1/2	up to 9 weeks	Terminal elimination half-life of Pharmacokinetic
Pharmacokinetic-AUC0-t	up to 9 weeks	Area under the plasma concentration-time curve of Pharmacokinetic
Pharmacokinetic-AUC0-∞	From first dose up to C3D1, estimated up to 9 weeks	Area under the plasma concentration-time curve of Pharmacokinetic
Pharmacokinetic-AUC0-τ	up to 9 weeks	Area under the plasma concentration-time curve of Pharmacokinetic
Pharmacokinetic-CL/F	up to 9 weeks	Apparent clearance of Pharmacokinetic
Pharmacokinetic-Vz/F	up to 9 weeks	Apparent volume of distribution in the terminal phase of Pharmacokinetic
Objective response rate (ORR)	12 months	The incidence of confirmed complete response or partial response.
Progression-free survival (PFS)	12 months	The time from the first dose of study treatment to PD or death for any reason, whichever comes first.
Disease control rate (DCR)	12 months	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.
Time to response (TTR)	12 months	The time from the first dose of HMPL-653 to the first objective response.
Duration of response (DoR)	12 months	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.
Overall survival (OS)	24 months	The time from the first dose of study treatment to death for any reason.

Trial Locations

Locations (5)

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, China

Harbin Medical University Cancer Hospital; 🇨🇳 Harbin, China

Jilin Provincial Cancer Hospital; 🇨🇳 Chang chun, China

Linyi Cancer Hospital; 🇨🇳 Linyi, China

Henan Cancer Hospital; 🇨🇳 Zhengzhou, China