Advanced Intrahepatic CholangiocarcinomaPhase 2/3NCT04353375
HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma
A Phase 2/3 study testing HMPL-453 in people with Advanced Intrahepatic Cholangiocarcinoma and Solid Tumor, Adult, run by Hutchmed at 1 site in China.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Intrahepatic Cholangiocarcinoma, Solid Tumor, Adult
- What is being tested?
- HMPL-453
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 235 participants
- Where
- 1 siteChina
- Study dates
- 3 Sep 2020to 28 Feb 2030
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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;
- Clinically significant arrhythmia or conduction abnormalities requiring clinical intervention;
- Patients with known deep venous thrombosis, treated with low molecular weight heparin (LMWH) or drugs with similar efficacy, and the investigator judges that the thrombosis is stable for ≥ 2 weeks ;
- Toxicities caused by prior anti-tumor treatment have not recovered to grade 0 or 1;
- The patient has any current disease or condition that affects drug absorption, or the patient cannot be orally administered;
- Combined with other malignant tumor or a history of other malignant tumor within 5 years prior to study screening;
- Patients currently has central nervous system metastases, meningeal metastases or spinal cord compression, except in individual cases;
- Any other medical condition or clinically significant laboratory abnormalities judged by the investigator would make the patients unsuitable to participate in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Chinese PLA General Hospital
Beijing, Beijing Municipality
Jianming Xu, +86 010-68182255, jmxu2003@163.com
About this study
Official title: An Open-Label, Single-Arm, Multicenter Phase 2/3b Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of HMPL-453 Tartrate in Patients With Advanced Intrahepatic Cholangiocarcinoma Habouring FGFR2 Fusion/Rearrangement
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.]
Read the detailed description
This is an open-label, single-arm, multicenter phase 2/3b clinical study to evaluate the efficacy and safety of HMPL-453 tartrate in the treatment of patients with advanced ICC habouring FGFR2 fusions/rearrangements/mutations. The study consists of the following 4 cohorts.
Cohort 1: Approximately 12 patients with locally advanced unresectable or metastatic ICC habouring 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 ICC habouring 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 enrolled patients, and after reaching an agreement with China Center for Drug Evaluation on 17 Feb 2023, approximately 87 patients with locally advanced unresectable or metastatic ICC habouring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance will be 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.
Cohort 3 (Confirmatory Study Cohort): A total of approximately 87 patients with locally advanced unresectable or metastatic ICC harbouring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance are planned to be enrolled in this cohort, as the confirmatory study phase of this study. Patients will receive HMPL-453 tartrate 300 mg QD for 14 days (Days 1 to 14), followed by 7 days off (Days 15 to 21), (21-day treatment cycles).
Cohort 4 (Exploratory Cohort): Approximately 10 to 20 treatment-naïve patients with locally advanced unresectable or metastatic ICC harbouring FGFR2 fusions/rearrangements/mutations are planned to be enrolled in this cohort. Patients will receive HMPL-453 tartrate 300 mg QD orally for 14 days (Days 1 to 14), followed by 7 days off (Days 15 to 21) (21-day treatment cycles).
- Being tested
- HMPL-453
- Keywords
- FGFR2 funsion, HMPL-453, ICC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMPL-453Drug
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)
| Study group | Role | What they receive |
|---|---|---|
| HMPL-453 | Experimental | HMPL-453 150mg QD HMPL-453 300mg QD Receives: Drug: HMPL-453 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
Proportion of patients whose best overall response are confirmed CR or PR
Measured: 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)
Proportion of patients whose best overall response after treatment is confirmed CR or PR, or judged as SD (SD≥6 weeks)
Measured: 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)
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: 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)
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: 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)
The time from the first study treatment to the onset of PD or death from any cause
Measured: 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)
The time from the patients receiving the first study drug until the death due to any cause
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2020
- Study start3 Sep 2020
- Primary completion30 Jun 2028 (estimated)
- Study completion28 Feb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Intrahepatic CholangiocarcinomaStudies of the same condition, open and under way.
- More trials run by HutchmedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 235 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hutchmed
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jianming Xu, PhD, Principal investigator, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04353375
- Sponsor's protocol ID
- 2019-453-00CH2
- Status last verified
- Dec 2025
- First submitted
- 16 Apr 2020
- Last updated
- 31 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Single-Arm, Multicenter Phase 2/3b Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of HMPL-453 Tartrate in Patients With Advanced Intrahepatic Cholangiocarcinoma Habouring FGFR2 Fusion/Rearrangement
- ClinicalTrials.gov ID
- NCT04353375
- Acronym / sponsor ID
- 2019-453-00CH2
- Keywords
- FGFR2 funsion, HMPL-453, ICC
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 235 participants (estimated)
- Lead sponsor
- HutchmedIndustry (pharma, biotech, devices)
- Study start
- 3 Sep 2020 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 28 Feb 2030 (estimated)
- First posted
- 20 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.]
Detailed description
This is an open-label, single-arm, multicenter phase 2/3b clinical study to evaluate the efficacy and safety of HMPL-453 tartrate in the treatment of patients with advanced ICC habouring FGFR2 fusions/rearrangements/mutations. The study consists of the following 4 cohorts.
Cohort 1: Approximately 12 patients with locally advanced unresectable or metastatic ICC habouring 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 ICC habouring 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 enrolled patients, and after reaching an agreement with China Center for Drug Evaluation on 17 Feb 2023, approximately 87 patients with locally advanced unresectable or metastatic ICC habouring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance will be 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.
Cohort 3 (Confirmatory Study Cohort): A total of approximately 87 patients with locally advanced unresectable or metastatic ICC harbouring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance are planned to be enrolled in this cohort, as the confirmatory study phase of this study. Patients will receive HMPL-453 tartrate 300 mg QD for 14 days (Days 1 to 14), followed by 7 days off (Days 15 to 21), (21-day treatment cycles).
Cohort 4 (Exploratory Cohort): Approximately 10 to 20 treatment-naïve patients with locally advanced unresectable or metastatic ICC harbouring FGFR2 fusions/rearrangements/mutations are planned to be enrolled in this cohort. Patients will receive HMPL-453 tartrate 300 mg QD orally for 14 days (Days 1 to 14), followed by 7 days off (Days 15 to 21) (21-day treatment cycles).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HMPL-453 | Experimental | Drug: HMPL-453HMPL-453 150mg QD HMPL-453 300mg QD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (22 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HMPL-453Cohort_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) | Drug | HMPL-453 |
Primary outcome
Overall response rate (ORR)
Time frame: 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
Proportion of patients whose best overall response are confirmed CR or PR
5 secondary outcomes
Disease control rate (DCR)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jianming Xu, PhD principal investigator
Chinese PLA General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing HMPL-453 in people with Advanced Intrahepatic Cholangiocarcinoma and Solid Tumor, Adult, run by Hutchmed at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bo Zhang (+86 21 2067 1819, boz@hutch-med.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2025.