HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma

Prior treatment

• 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;
• Using a strong inducer or inhibitor of cytochrome P450 3A (CYP3A) within 2 weeks or 5 half-lives of the study treatment;
• Active infection requiring systemic treatment within 1 week prior to the start of the study treatment;
• Prior history of retinal detachment, or current diseases that may cause retinal detachment;
• 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;

Other illness

• 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;
• Clinically significant arrhythmia or conduction abnormalities requiring clinical intervention;
• 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;

Lab values

• 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;
• Screening blood phosphorus levels above ULN, or history of abnormal calcium phosphorus metabolism requiring clinical intervention or relevant medical history;
• Any other medical condition or clinically significant laboratory abnormalities judged by the investigator would make the patients unsuitable to participate in this study.

Other

• Currently keratopathy confirmed by ophthalmological examination;
• Patients currently has central nervous system metastases, meningeal metastases or spinal cord compression, except in individual cases;

• 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.