Phase 2 Study of HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma

Advanced Intrahepatic Cholangiocarcinoma Clinical Trial

Official title:

An Open-Label, Single-Arm, Multicenter Phase 2 Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of HMPL-453 Tartrate in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusion/Rearrangement

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04353375
• Other study ID #: 2019-453-00CH2
• Status: Recruiting
• Phase: Phase 2
• Start date: September 3, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2023
• Source: Hutchmed
• Contact: Bo Zhang
• Phone: +86 21 2067 1819
• Email: boz[@]hutch-med.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 harboring 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.]

Description:

This is an open-label, single-arm, multicenter phase 2 clinical study to evaluate the efficacy and safety of HMPL-453 tartrate in the treatment of patients with advanced ICC harboring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance. The study consists of cohort 1 and cohort 2.

Cohort 1: Approximately 12 patients with locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance are planned to be enrolled in this cohort to receive HMPL-453 tartrate 150 mg administered orally once daily (QD) continuously in 21-day cycles.

Cohort 2: A total of approximately 113-116 patients are planned to be enrolled in this cohort, divided into safety run-in and extension phases. Approximately 6 to 9 patients with solid tumors who failed standard treatment or had intolerable toxicity will be enrolled into the first phase (safety run-in phase), to receive 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). Dose limiting toxicities (DLT) observation period consists of 28 days, in which a cycle of treatment will be received. Patients will enter second stage of cohort 2 (extension phase) after completion of safety run-in assessments. Approximately 20 patients with locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance will receive HMPL-453 tartrate 300 mg QD orally administered (for 14 consecutive days [Day 1 to 14], followed by 7 days off [Day 15 to 21], 21 days as a treatment cycle). Based on the efficacy and safety data of the already enrolled patients, and after reaching an agreement with China Center for Drug Evaluation, approximately 90 additional patients with locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance are being enrolled to support registration submission as the registration study stage of this study, receiving 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 128
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed the informed consent form;

2. Age = 18 years;

3. Patients with histologically or cytologically confirmed locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma with FGFR2 fusions/rearrangements;

4. Patients have received at least one prior systemic treatment regimen for advanced intrahepatic cholangiocarcinoma and have intolerable PD or toxicity ;

5. Measurable lesion according to RECIST v1.1, refer to the protocol

6. ECOG performance status of 0 or 1;

7. Female patients or male patients with partners of childbearing potential must take effective contraceptive measures per the protocol.

Exclusion Criteria:

1. Patients who previously received selective FGFR targeting therapy;

2. Received approved or researched systemic anti-tumor treatment within 3 weeks;

3. Radical radiotherapy within 4 weeks;

4. Have received local anti-tumor treatment within 4 weeks;

5. Major surgery requiring hospitalization or incomplete healing of the surgery incision within 4 weeks;

6. Current or prior history of retinal detachment;

7. Clinically significant cardiovascular disease such as congestive heart failure or arrhythmia;

8. Patients with acute or chronic active hepatitis B or C infection;

9. The patients with human immunodeficiency virus (HIV) infection;

10. Active infection requiring systemic treatment within 1 week;

11. History of significant abnormal calcium phosphorus metabolism;

12. Currently keratopathy confirmed by ophthalmological examination;

13. Toxicities caused by prior anti-tumor treatment have not recovered to grade 0 or 1;

14. Patients who in the opinion of the investigator may be unsuitable for participating in the study;

15. Combined with other malignant tumor or a history of other malignant tumor;

16. Patients currently has central nervous system metastases, meningeal metastases or spinal cord compression.

Related Conditions & MeSH terms

• Advanced Intrahepatic Cholangiocarcinoma
• Cholangiocarcinoma

Intervention

Drug:
• HMPL-453
Cohort_1:HMPL-453 150mg QD continuously in 21-day cycles; Cohort_2: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)

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Hutchmed

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Disease control rate (DCR)	Proportion of patients whose best overall response after treatment is confirmed CR or PR, or judged as SD (SD=6 weeks)	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	Time to response (TTR)	The time from the first dose of study drug to the first CR or PR in patients whose best overall response is a 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	Duration of response (DoR)	The time from initial CR or PR to PD or death from any cause, whichever comes first, in patients whose best overall response is a 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	Progression-Free Survival (PFS)	The time from the first study treatment to the onset of PD or death from any cause	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	Overall survival (OS)	The time from the patients receiving the first study drug until the death due to any cause	up to 2 years