Actively Recruiting
A Phase 2 Open-Label Study of Irpagratinib with Atezolizumab and Bevacizumab in Patients with Advanced or Unresectable Hepatocellular Carcinoma
Led by Asan Medical Center · Updated on 2026-03-18
33
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
A
Asan Medical Center
Lead Sponsor
A
Abbisko Therapeutics Co, Ltd
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, tolerability, and effectiveness of combining Irpagratinib with Atezolizumab and Bevacizumab in patients with advanced or unresectable hepatocellular carcinoma (HCC) that shows FGF19 overexpression. This phase 2, open-label study includes two parts: a Safety Run-in to identify a safe dose of Irpagratinib for the combination, and an Expansion phase to further assess safety and preliminary effectiveness based on Simon's two-stage design. During the Safety Run-in, patients receive Irpagratinib orally at either 150 mg or 200 mg twice daily in repeated 21-day cycles, along with Atezolizumab 1200 mg and Bevacizumab 15 mg/kg administered intravenously every three weeks. Dose-limiting toxicities (DLTs) are monitored during the first cycle to decide the recommended Irpagratinib dose for the Expansion phase. In the Expansion phase, up to 24 patients receive the selected Irpagratinib dose combined with Atezolizumab and Bevacizumab every three weeks. Patients who stop one of the treatments due to side effects may continue the others if clinical benefit is observed. Participants will undergo regular imaging, lab tests, and clinical assessments to monitor their response and safety throughout treatment cycles lasting 21 days. The study's primary outcomes include the incidence of DLTs after the first cycle and the objective response rate over an average of 21 months. Secondary outcomes include progression-free survival, disease control rate, duration of response, time to progression, overall survival, and safety events. Follow-up for survival continues every 12 weeks for up to one year after the last treatment dose.
CONDITIONS
Brief Title
A Prospective Study to Evaluate the Safety and Efficacy of the Combination Therapy of Irpagratinib, Atezolizumab, and Bevacizumab in Patients With Hepatocellular Carcinoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patient is able to understand, sign, and date informed consent and comply with study procedures
- Male or female aged 19 years or older at consent
- Histologically or cytologically confirmed advanced or unresectable hepatocellular carcinoma not suitable for surgery or local therapies
- Positive test for FGF19 overexpression from primary liver lesion tissue
- Barcelona Clinic Liver Cancer stage B or C with Child-Pugh score 5 to 6, no hepatic encephalopathy, and no clinically significant ascites
- At least one target lesion measurable by RECIST v1.1
- ECOG performance status of 0 or 1
- Life expectancy of at least 3 months
- Adequate organ and blood function per specified laboratory values within 14 days prior to treatment
- Use of effective birth control for non-surgically sterilized patients of childbearing potential during and up to 6 months after treatment
- Negative pregnancy test for applicable female patients within 14 days prior to treatment
You will not qualify if you...
- Prior systemic chemotherapy for advanced/unresectable HCC except up to one cycle of Atezolizumab plus Bevacizumab
- Prior therapy with immune checkpoint inhibitors or immune stimulatory agents
- Previous treatment with FGFR inhibitors
- Locoregional liver therapy within 4 weeks before study treatment
- Major surgery or radiotherapy with significant marrow exposure within specified timeframes
- Unresolved toxicities from prior cancer therapies above Grade 1 except specified exceptions
- Use of certain CYP3A4 inhibitors or inducers within 14 days prior to treatment
- Systemic corticosteroids or immunosuppressants within 2 weeks prior or planned during trial except low-dose prednisone
- Live vaccine administration within 4 weeks prior or during trial (inactivated vaccines allowed)
- Chronic daily NSAID use
- Active infection or fever over 38.5°C or recent antibiotic treatment
- Known fibrolamellar carcinoma, sarcomatoid HCC, or mixed hepatocellular cholangiocarcinoma
- Active central nervous system metastasis
- Metastatic disease involving major airways, blood vessels, or large mediastinal masses
- Uncontrolled ascites, pleural or pericardial effusion requiring intervention
- History of hepatic encephalopathy
- Liver tumor involvement 50% or greater
- Advanced portal vein tumor thrombus (Vp4) or beyond
- High-risk or recent bleeding from esophageal or gastric varices
- Recent core biopsy or minor surgery within 3 days before Bevacizumab
- History of abdominal or tracheoesophageal fistula, GI perforation, or abscess within 6 months
- Second primary malignancy within 5 years except low-risk cancers
- Allergy or severe hypersensitivity to study drugs or related components
- History of autoimmune disease except controlled thyroid or mild skin conditions
- Prolonged QTc interval or significant ECG abnormalities
- Reduced left ventricular ejection fraction below 50%
- Significant cardiac disease or uncontrolled hypertension
- Recent significant vascular disease
- Serious infections requiring systemic therapy
- Immunodeficiency including HIV or active tuberculosis
- HBV or HCV infection not adequately controlled or requiring treatment
- Other significant comorbidities affecting safety or compliance
- History of stem cell or organ transplantation
- Recent hemoptysis
- Bleeding disorders or use of certain anticoagulants or antiplatelet agents
- Non-healing wounds, active ulcers, or untreated fractures
- Inability to take oral medication or conditions affecting absorption
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - At least 1 cycle of 21 days
Participants receive oral Irpagratinib daily in repeated 21-day cycles, plus Atezolizumab and Bevacizumab intravenously every 3 weeks. The safety and tolerability are evaluated during the first 21-day cycle.
Weekly visits during Cycle 1
Duration - Repeated 21-day cycles until intolerable toxicity or disease progression
Participants receive Irpagratinib orally in 21-day cycles combined with Atezolizumab 1200 mg IV and Bevacizumab 15 mg/kg IV every 3 weeks. Treatment continues until intolerable toxicity or disease progression.
Visits every 3 weeks for IV infusions and oral medication monitoring
Duration - Up to 1 year after treatment
Participants are monitored for overall survival and safety for up to 1 year after the last dose of study treatment.
Visits every 12 weeks
Trial Site Locations
Total: 1 location
1
Asan Medical Center,
Seoul, South Korea
Actively Recruiting
Research Team
C
Changhoon Yoo
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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