HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma

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.\]

Eligibility

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.

Conditions3

Browse More Trials