A Prospective Study to Evaluate the Safety and Efficacy of the Combination Therapy of Irpagratinib, Atezolizumab, and Bevacizumab in Patients With Hepatocellular Carcinoma

Recruiting now · Phase 2

Conditions studied: Carcinoma, Hepatocellular

In brief

This is a phase 2, open-label study to evaluate the safety, tolerability and efficacy of Irpagratinib in combination with Atezolizumab and Bevacizumab in patients with advanced or unresectable HCC harboring FGF19 overexpression. 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 efficacy and safety using Simon's two-stage design.

Key facts

Study ID

NCT07010497

Run by

Asan Medical Center

People needed

33

Starts

2026-03-16

Expected to finish

2029-03-31

Last updated by the study team

2026-07-15

Who can join

Age: 19 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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:
• 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.
• 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.
• 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.
• 4.ECOG performance status score 0-1
• 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/Lb) Platelet count (PLT) ≥75×109/Lc) Hemoglobin (Hb) ≥85g/L (8.5g/dL)d) Total bilirubin (TBIL) ≤3×ULNe) Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 5 ×ULNf) Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (Crcl) ≥50 mL/min based on Cockcroft-Gault formulag) 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 β-HCG test result within 14 days before first administration.

You may not qualify if…

• 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 (eg, anti-PD-1, anti-PD-L1/2, anti-CTLA-4, anti-TIGIT, OX-40, or CD137). Patients has received one cycle of Atezolizumab plus Bevacizumab is eligible for this trial.
• 3. Previous treatment with FGFR inhibitors including selective FGFR4 or pan-FGFR inhibitors.
• 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 <4 weeks; endocrine therapy with anti-tumor indications for < 2 weeks.
• 6. Prior toxicities from radiotherapy and other anti-cancer therapies that have not recovered to Grade ≤1 (CTCAE v5.0) except for which eligibility criteria allowed, alopecia, vitiligo, hormone replacement therapy controlled stable hypothyroidism, and Grade ≤2 neurotoxicity or toxicities related to prior one cycle of Atezolizumab plus Bevacizumab that investigator believes don't affect patients and safety assessment.
• 7. Concomitant use of P-gp transporter inhibitors; as well as moderate or strong inhibitors or inducers of CYP3A4 (including grapefruit juice, grapefruit hybrids, pomegranates, starfruits, pomelos, Seville oranges or juice or products) within at least 14 days prior to the first dose of the study drug.
• 8. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to initiation of study treatment, or anticipated requirement for systemic immunosuppressive medications during the trial (except for patients who received one-time, acute, low-dose prednisone <7.5 mg/d or equivalent corticosteroids).
• 9. Vaccination with a live, attenuated vaccine within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivate vaccines (e.g., COVID-19 vaccines, inactivated influenza vaccines).
• 10. Chronic daily treatment with a nonsteroidal anti-inflammatory drug (NSAID). Occasional use of NSAIDS for the symptomatic relief of medical conditions such as headache or fever is allowed.
• 11. Active infection or unexplained fever > 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 pericardial effusion requiring intervention within 2 weeks before administration of study treatment.
• 16. History of hepatic encephalopathy.
• 17. Liver tumor as a percentage of liver ≥ 50% as judged by the investigator.
• 18. Vp4 type portal vein tumor thrombus and beyond (such as inferior vena cava).
• 19. Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding or a prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
• 20. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to the first dose of Bevacizumab.
• 21. History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to initiation of study treatment.
• Diagnostic Assessments
• 22. History of second primary malignancy other than HCC within 5 years prior to screening, except for malignancies with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, etc.

Where it is running

• Asan Medical Center, — Seoul, South Korea (enrolling)
• Seoul National University Hospital — Seoul, South Korea
• Severance Hospital — Seoul, South Korea

Full record on ClinicalTrials.gov

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