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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignant Solid Tumors; TGCT
• Intervention / Treatment: Drug: HMPL-653

• Study Type: Interventional
• Enrollment (Anticipated): 113
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cindy Hua; Phone Number: +86 21 2067 3221; Email: cindyh@hutch-med.com
• Study Contact Backup: Name: Dan Yu; Phone Number: 5927 +86 10 8518 8690; Email: Dany@hutch-med.com

Study Locations

• China
  • Chang chun, China
    • Recruiting
    • Jilin Provincial Cancer Hospital
    • Contact: Ying Cheng, Prof
  • Harbin, China
    • Not yet recruiting
    • Harbin Medical University Cancer Hospital
    • Contact: Yanqiao Zhang, Prof
  • Linyi, China
    • Not yet recruiting
    • Linyi Cancer Hospital
    • Contact: Jianhua Shi, Prof
  • Zhengzhou, China
    • Not yet recruiting
    • Henan Cancer Hospital
    • Contact: Suxia Luo, Prof
  • Zhengzhou, China
    • Not yet recruiting
    • The First Affiliated Hospital of Zhengzhou University
    • Contact: Weijie Zhang, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: HMPL-653 open-label treatment arm; 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.

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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited
• Investigators: Principal Investigator: Ying Cheng, Prof, Jilin Provincial Cancer Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 18, 2022
• Primary Completion (ANTICIPATED): June 28, 2024
• Study Completion (ANTICIPATED): April 14, 2025

Study Registration Dates

• First Submitted: February 6, 2022
• First Submitted That Met QC Criteria: March 11, 2022
• First Posted (ACTUAL): March 14, 2022

Study Record Updates

• Last Update Posted (ACTUAL): March 14, 2022
• Last Update Submitted That Met QC Criteria: March 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 2021-653-00CH1

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