Evaluating HMPL-453 for advanced intrahepatic cholangiocarcinoma

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

This study is testing a new drug called HMPL-453 to see if it helps people with advanced bile duct cancer that has specific genetic changes.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 235 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hutchmed (Industry-sponsored)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT04353375 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the efficacy and safety of HMPL-453 tartrate in patients with advanced intrahepatic cholangiocarcinoma that have FGFR2 fusions or rearrangements. Participants will receive HMPL-453 orally for 14 days followed by a 7-day break, in a 21-day treatment cycle. The study includes two cohorts: one for patients with locally advanced unresectable or metastatic disease after prior treatment failure, and another for safety assessments before extending to a larger group. The primary goal is to evaluate the objective response rate in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed advanced intrahepatic cholangiocarcinoma and FGFR2 fusions/rearrangements who have experienced treatment failure or intolerable toxicity from prior systemic therapies.

Not a fit: Patients who have previously received selective FGFR targeting therapy or those with certain recent treatments or surgeries may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced intrahepatic cholangiocarcinoma who have limited treatment options.

How similar studies have performed: While this approach is focused on a specific genetic alteration, similar studies targeting FGFR pathways have shown promise in other cancers, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Have fully understood the study and voluntarily signed the ICF;
2. Age ≥ 18 years;
3. 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)
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)
5. Measurable lesion according to RECIST v1.1;
6. ECOG performance status of 0 or 1;
7. Life expectancy ≥ 12 weeks;
8. 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 prior to the start of the study treatment;
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. Using a strong inducer or inhibitor of cytochrome P450 3A (CYP3A) within 2 weeks or 5 half-lives of the study treatment;
8. 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;
9. International normalized ratio above 1.5 or partial activated prothrombin time above 1.5 times ULN;
10. History of clinically significant active hepatopathy, including active viral hepatitis, or other active hepatitis, clinically significant moderate to severe liver cirrhosis;
11. The patients with human immunodeficiency virus (HIV) infection;
12. Active infection requiring systemic treatment within 1 week prior to the start of the study treatment;
13. Screening blood phosphorus levels above ULN, or history of abnormal calcium phosphorus metabolism requiring clinical intervention or relevant medical history;
14. Currently keratopathy confirmed by ophthalmological examination;
15. Prior history of retinal detachment, or current diseases that may cause retinal detachment;
16. Clinically significant arrhythmia or conduction abnormalities requiring clinical intervention;
17. 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 ;
18. Toxicities caused by prior anti-tumor treatment have not recovered to grade 0 or 1;
19. The patient has any current disease or condition that affects drug absorption, or the patient cannot be orally administered;
20. Combined with other malignant tumor or a history of other malignant tumor within 5 years prior to study screening;
21. Patients currently has central nervous system metastases, meningeal metastases or spinal cord compression, except in individual cases;
22. Any other medical condition or clinically significant laboratory abnormalities judged by the investigator would make the patients unsuitable to participate in this study.

Where this trial is running

Beijing, Beijing Municipality

• Chinese PLA General Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Jianming Xu, PhD — Chinese PLA General Hospital
• Study coordinator: Bo Zhang

Conditions Advanced Intrahepatic Cholangiocarcinoma; Solid Tumor, Adult; FGFR2 funsion; HMPL-453; ICC