HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma

NCT04353375 | Recruiting Phase 2

• 1 other identifier: 2019-453-00CH2
• Study Type: interventional
• Target: 235
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate in patients with advanced intrahepatic cholangiocarcinoma harboring FGFR2 fusion/rearrangement. The main questions it aims to answer are: To evaluate the objective response rate (ORR) of HMPL-453 tartrate in the treatment of patients with advanced intrahepatic cholangiocarcinoma (ICC) habouring fibroblast growth factor receptor (FGFR) 2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance Participants will receive HMPL-453 tartrate 300 mg QD orally (for 14 consecutive days \[Days 1 to 14\] followed by 7 days off \[Day 15 to 21\], 21 days as a treatment cycle.\]

Conditions

Advanced Intrahepatic Cholangiocarcinoma; Solid Tumor, Adult

Keywords

FGFR2 funsion; HMPL-453; ICC

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Proportion of patients whose best overall response are confirmed CR or PR

  Measured up to 6 months after the last patient has been enrolled or all patients have finished their last PFS follow up, whichever comes first

Secondary Outcomes (5)

• Disease control rate (DCR)

  Measured up to 6 months after the last patient has been enrolled or all patients have finished their last PFS follow up, whichever comes first

• Time to response (TTR)

  Measured up to 6 months after the last patient has been enrolled or all patients have finished their last PFS follow up, whichever comes first

• Duration of response (DoR)

  Measured up to 6 months after the last patient has been enrolled or all patients have finished their last PFS follow up, whichever comes first

• Progression-Free Survival (PFS)

  Measured up to 6 months after the last patient has been enrolled or all patients have finished their last PFS follow up, whichever comes first

• Overall survival (OS)

  up to 2 years

Study Arms (1)

HMPL-453

EXPERIMENTAL

HMPL-453 150mg QD HMPL-453 300mg QD

Drug: HMPL-453

Interventions

HMPL-453 DRUG

Cohort\_1:HMPL-453 150mg QD continuously in 21-day cycles; Cohort\_2, Cohort\_3 and Cohort\_4:HMPL-453 tartrate 300 mg QD orally (for 14 consecutive days \[Day 1 to 14\], followed by 7 days off \[Day 15 to 21\], 21 days as a treatment cycle)

HMPL-453

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have fully understood the study and voluntarily signed the ICF;
• Age ≥ 18 years;
• a. pathologically or cytologically confirmed advanced treatment failure solid tumor with standard patients (applicable to cohorts2 stage I); b. histologically or cytologically confirmed histologically or cytologically confirmed locally advanced unresectable or metastatic ICC patients with FGFR2 fusions/rearrangements/mutation (applicable to Cohort 1, Cohort 2 Stage II, Cohort 3 and Cohort 4)
• a. The patients have received at least one prior systemic treatment regimen for advanced ICC and has intolerable PD or toxicity(Cohort1-3); b. Patients who have not received any prior systemic therapy for advanced ICC(Cohort4)
• Measurable lesion according to RECIST v1.1;
• ECOG performance status of 0 or 1;
• Life expectancy ≥ 12 weeks;
• Female patients or male patients with partners of childbearing potential must take effective contraceptive measures per the protocol.

You may not qualify if:

• Patients who previously received selective FGFR targeting therapy;
• Received approved or researched systemic anti-tumor treatment within 3 weeks prior to the start of the study treatment;
• Radical radiotherapy within 4 weeks;
• Have received local anti-tumor treatment within 4 weeks;
• Major surgery requiring hospitalization or incomplete healing of the surgery incision within 4 weeks;
• Current or prior history of retinal detachment;
• Using a strong inducer or inhibitor of cytochrome P450 3A (CYP3A) within 2 weeks or 5 half-lives of the study treatment;
• Taking drugs or dietary supplementsthat may cause blood phosphorus and/or blood calcium to rise within 2 weeks prior to the start of the study treatment;
• International normalized ratio above 1.5 or partial activated prothrombin time above 1.5 times ULN;
• History of clinically significant active hepatopathy, including active viral hepatitis, or other active hepatitis, clinically significant moderate to severe liver cirrhosis;
• The patients with human immunodeficiency virus (HIV) infection;
• Active infection requiring systemic treatment within 1 week prior to the start of the study treatment;
• Screening blood phosphorus levels above ULN, or history of abnormal calcium phosphorus metabolism requiring clinical intervention or relevant medical history;
• Currently keratopathy confirmed by ophthalmological examination;
• Prior history of retinal detachment, or current diseases that may cause retinal detachment;

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, China

RECRUITING

Study Officials

• Jianming Xu, PhD

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bo Zhang

CONTACT

+86 21 2067 1819; boz@hutch-med.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2020
• First Posted: April 20, 2020
• Study Start: September 3, 2020
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): February 28, 2030
• Last Updated: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)