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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Malignant Solid Tumors, TGCT

Intervention / Treatment
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* Drug: HMPL-653


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand and willing to sign the ICF. Aged 18 to 75 years. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy at least 12 weeks. Adequate bone marrow, liver and kidney function. Exclusion Criteria: Toxicity associated with previous antitumor therapy not recovered to ≤CTCAE grade 1； Previous treatment with anti-CSF1R therapy and have progressive disease; Receiving approved systematic antitumor therapy or in the treatment period of other interventional clinical study within 4 weeks prior to the first dose. Patients with central nervous system (CNS) malignant tumor or malignant solid tumor with known CNS metastasis; Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HMPL-653 open-label treatment arm<br>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<br>* 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.<br>|

What is the study measuring?
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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 |