A Study of HMPL-453 in Patients With Advanced Solid Malignancies

NCT ID: NCT03160833

Last Updated: 2020-02-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-23
• Study Completion Date: 2020-06-30

Brief Summary

This is a dose escalation study consisting of two stages: Dose-escalation stage (stage 1): Patients will take a single dose of HMPL-453 on Day 1 and will be followed for one week for safety observations. After one week of observation, if no safety issues occur, patients can continue multiple dosing of HMPL-453 QD (quaque die) and start on the DLT (Dose Limited Toxicity) assessment cycles. Each cycle consists of 28-days. Patients are required to draw blood samples for PK and safety analysis at specific time points during the treatment; Dose-Expansion Stage (Stage 2): This stage is to further evaluate the safety, tolerability, PD (pharmacodynamics) profile, and preliminary anti-tumor activity of HMPL-453 at the RP2D (recommended phase 2 dose) in approximately 10 patients with advanced solid tumor.

Detailed Description

Dose-escalation stage (stage 1): Patients participating in the dose-escalation stage will take a single dose of HMPL-453 on Day 1 and will be followed for one week for safety observations. After one week of observation, if no safety issues occur, patients can continue multiple dosing of HMPL-453 QD and start on the DLT assessment cycles. Each cycle consists of 28-days. Patients are required to draw blood samples for PK and safety analysis at specific time points during the treatment.

The 3+3 design will be employed for the dose escalation and MTD ( maximum tolerated dose) determination. To limit the number of patients being exposed to potentially ineffective doses, one patient will be enrolled and dosed in the initial dose cohort. If there are no DLT or less than grade 2 toxicities of Common Terminology Criteria for Adverse Event ( CTC AE ) occur in the first treatment cycle, then the study will be escalated to the next dose cohort. Otherwise, the trial will revert to a standard 3+3 design.

Dose-Expansion Stage (Stage 2): This stage is to further evaluate the safety, tolerability, pharmacokinetics (PK) profile, and preliminary anti-tumor activity of HMPL-453 at the RP2D in approximately 60 patients with advanced solid tumor. Patients with FGFR ( Fibroblast Growth Factor Receptor) dysregulated advanced solid tumors, including but not limited to advanced urothelial bladder cancer, advanced cholangiocarcinoma (patients with cancers of the gallbladder or ampulla of Vater are not eligible) and others solid tumors are preferred to be enrolled.

Expansion stage will begin after dose-escalation stage is completed and the MTD/RP2D has been determined. Patients will receive HMPL-453 with 28-day treatment cycles until disease progression, death, intolerable toxicity, no longer benefiting from the study treatment per investigator's discretion, or withdrawal of consent, whichever comes first.

Conditions

Solid Tumor, Adult

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HMPL-453

Two strengths of HMPL-453 tablets (25 mg and 100 mg based on the free base) will be used for clinical studies. The drug products are coated tablets, which are packaged in white induction sealed HDPE (high-density polyethylene) bottles. HMPL-453 will be administered to patients as oral tablet(s) on a daily basis, until disease progression, intolerable toxicity, or death. Dose levels are to be potentially tested in this study include 50, 100, 200, 300, 400, and 500 mg/day

Group Type: EXPERIMENTAL

HMPL-453

Intervention Type: DRUG

oral administrative

Interventions

HMPL-453

oral administrative

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• In the dose escalation stage, patients with locally advanced, or metastatic solid tumor who have failed, or intolerable to, standard therapies or for whom no standard therapies exist will be enrolled.
• In the dose expansion stage, patients with locally advanced, or metastatic solid tumor and FGFR dysregulation who have failed or intolerable to standard therapies or no standard therapies exist are to be enrolled.
• In the dose escalation stage: evaluable or measurable disease according to RECIST Version 1.1. In the dose expansion stage: measurable disease according to RECIST Version 1.1.
• Life expectancy of at least 12 weeks.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.

Exclusion Criteria

• Prior or current treatment with any selective FGFR inhibitor.

• Minimum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchison Medipharma Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Weiss Yang, Doctor

Role: STUDY_DIRECTOR

HMPL

Locations

Beijing 307 Hospital

Beijing, Beijing Municipality, China

Cancer center of SYSU

Guangzhou, Guangdong, China

Countries

China

Other Identifiers

2015-453-00CH1

Identifier Type: -

Identifier Source: org_study_id