Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
HMPL-453 · 4 trials · 5 indications
Area under the plasma concentration - time curve from time 0 to time of last measurable concentration
Area under the plasma concentration - time curve from time 0 extrapolated to infinity
Peak concentration
DLT, TEAEs and SAEs
Objective response rate (ORR) in patients with the selected tumors along with certain FGFR gene alterations
| Arm | Type | Description |
|---|---|---|
| Part A:HMPL-453 with Itraconazole | OTHER | - |
| Part B:HMPL-453 with Rifampin | OTHER | - |
| dose escalation phase of HMPL-453 monotherapy or combination therapy | EXPERIMENTAL | HMPL-453 monotherapy or combination therapy |
| indication specific dose expansion phase of HMPL-453 monotherapy or combination therapy | EXPERIMENTAL | HMPL-453 monotherapy or combination chemotherapy, in patients with IHCC, G/GEJ, UC, and solid tumors harboring specific FGFR gene alterations |
| Name | Type | Description |
|---|---|---|
| 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) |
| Rabeprazole | DRUG | 20 mg of rabeprazole will be administered by mouth once daily. |
| HMPL-453 with Itraconazole | DRUG | HMPL-453: 100mg, D1、D14; Itraconazole: 400mg, D10;200mg,D11-D22 |
| HMPL-453 with Rifampin | DRUG | HMPL-453: 300mg, D1、D16; Rifampin: 600mg, D10-D24 |
| gemcitabine and cisplatin | DRUG | Gemcitabine and Cisplatin administered intravenously. |
| toripalimab | DRUG | Toripalimab administered intravenously. |
| Docetaxel | DRUG | Docetaxel administered intravenously. |
Inclusion Criteria: 1. Has fully understood and voluntarily signed the ICF for this study. 2. Male or female 18 years of age or older. 3. Body mass index (BMI) at screening: 18 \< BMI ≤ 29.9 kg/m 2 and weight ≥ 50 kg for men and ≥ 45 kg for women. 4. Female subjects of childbearing potential use hi...
HMPL-453 is an investigational small molecule being studied for advanced intrahepatic cholangiocarcinoma and other advanced solid tumors. It is also being evaluated in healthy volunteer studies examining drug interactions and food effects. The main clinical program focuses on patients with advanced intrahepatic cholangiocarcinoma, a form of bile duct cancer.
HMPL-453 is a small molecule inhibitor targeting FGFR1, FGFR2, and FGFR3, three fibroblast growth factor receptors. By inhibiting these receptor kinases, the drug is designed to interfere with FGFR-driven signaling in tumors. The clinical program is biomarker-selected, meaning patients are screened for relevant FGFR alterations before enrollment.
HMPL-453 is being developed by HUTCHMED (China) Limited, which trades under the ticker HCM. The company is running the clinical development program, including a Phase 2/Phase 3 study in advanced intrahepatic cholangiocarcinoma and earlier-phase studies in solid tumors and healthy volunteers.
HMPL-453 is in Phase 3 development. The lead trial, NCT04353375, is a Phase 2/Phase 3 study in advanced intrahepatic cholangiocarcinoma that is currently recruiting, with a planned enrollment of 235 participants. HMPL-453 is investigational and has not been approved for any indication.
HMPL-453 has been studied in several trials. NCT04353375 is a recruiting Phase 2/Phase 3 study in advanced intrahepatic cholangiocarcinoma. Completed studies include NCT05173142, a Phase 1b/2 trial in advanced solid tumors, NCT05930119, a food effect and PPI study, and NCT07697157, which examined interactions with itraconazole and rifampin in healthy volunteers.