None listed
Conditions
Interventions
Drug : This study composes two parts, a Safety Run-in part to evaluate safety and establish the dose of Irpagratinib for the triple combination, and an Expansion part to evaluate the preliminary effic
Sponsors
Asan Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol. 2. Male or female, aged =19 at the time of signing inform consent form. 3. Patients must have histological or cytological confirmed advanced or unresectable HCC not amenable to curative surgical or loco-regional therapies. And patients must satisfy: 1) Provide archived tissue sample for FGF19 overexpression detection. For Safety-Run in and Expansion: the result of FGF19 overexpression lab testing must be positive as defined. Only tissue from primary lesion of liver is eligible. 2) Barcelona Clinic Liver Cancer (BCLC) stage B or C and Child-Pugh score 5~6 without hepatic encephalopathy, no clinically apparent ascites or require medical intervention. (Refer to Appendix 3. and Appendix 4.) 3) Have at least 1 target lesion (per RECIST v1.1). Patients who received prior local therapy (e.g., radiofrequency ablation, percutaneous injection, cryoablation, high-intensity focused ultrasound, transarterial (chemo) embolization, etc.) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed per RECIST v1.1. (Refer to Appendix 5.) 4. ECOG performance status score 0-1 (Refer to Appendix 6.) 5. Life expectancy = 3 months 6. Adequate organ and hematologic function as indicated by the following screening assessments performed within 14 days prior to the first administration (without blood transfusion, or medication with stimulation factors or thrombopoietin receptor agonists (TPO-RAs) within 14 days before blood sample collection): a) Absolute neutrophil count (ANC) =1.0×109/L b) Platelet count (PLT) =75×109/L c) Hemoglobin (Hb) =85g/L (8.5g/dL) d) Total bilirubin (TBIL) =3×ULN e) Aspartate transaminase (AST) and alanine transaminase (ALT) = 5 ×ULN f) Serum creatinine (Cr) =1.5×ULN or creatinine clearance (Crcl) =50 mL/min based on Cockcroft-Gault formula g) For patients not receiving therapeutic anticoagulation: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) =2×ULN. h) Urinalysis for proteinuria <2+ (patients discovered to have =2+ proteinuria on urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate <1g of protein in 24 hours) 7. Non-surgically sterilized male or female patients of childbearing potential must agree to use effective methods of birth control during the study and for up to 6 months after the last dose of study drug. Non-surgically sterilized female patients of childbearing potential must in non-lactation period and have a negative ß-HCG test result within 14 days before first administration.
Exclusion criteria
Exclusion criteria: Prior/Concomitant Therapy 1. Has received any systemic chemotherapy, including anti-VEGF therapy, or any systemic investigational anticancer agents for advanced/unresectable HCC. Patient who has received one cycle of Atezolizumab plus Bevacizumab is eligible for this trial. 2. Has received prior therapy with immune checkpoint inhibitors or immune stimulatory agents (e.g., anti-PD-1, anti-PD-L1/2, anti-CTLA-4, anti-TIGIT, OX-40, or CD137). Patients who have received one cycle of Atezolizumab plus Bevacizumab are eligible for this trial. 3. Previous treatment with FGFR inhibitors including selective FGFR4 or pan-FGFR inhibitors. (Refer to Appendix 7.) 4. Has received locoregional therapy to liver (transcatheter chemoembolization, transcatheter embolization, hepatic arterial infusion, radiation, radioembolization, or ablation) within 4 weeks prior to the first dose of study intervention. 5. Previous anti-cancer therapy prior to initiation of study treatment: major surgery (except palliative therapy), radiotherapy (bone-marrow exposure >30%), loco-regional treatment 38.5? or last treatment with therapeutic oral or intravenous antibiotics within 2 weeks prior to the first dose of study treatment. Factors related to the disease 12. Known fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma. 13. Has a known active central nervous system (CNS) metastasis. 14. Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses (<30 mm from the carina) of large volume. Patients with vascular invasion of the portal or hepatic veins may be enrolled. 15. Patients with refractory/uncontrolled ascites, pleural effusion or perica
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Run-in: Incidence of DLTs in Cycle 1;Expansion: Objective response rate (ORR) determined by the investigator according to RECIST v1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) according to RECIST v1.1;Disease control rate (DCR) according to RECIST v1.1;Duration of response (DOR) according to RECIST v1.1;Time to progression (TTP);Overall survival (OS);Incidence and severity of adverse events (AEs), and serious adverse events (SAEs) | — |
Countries
Korea, Republic of
Contacts
Public ContactJIYUN AN
Asan Medical Center
Outcome results
None listed