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

NCT07010497 | Recruiting Phase 2

• 1 other identifier: ABSK-011-2001
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (2)

• Incidence of DLTs

  Safety Run-in: Incidence of DLTs in Cycle 1

  Safety Run-in: At the end of Cycle 1 (each cycle is 21 days)

• Objective response rate (ORR)

  Expansion: Objective response rate (ORR) determined by the investigator according to RECIST v1.1

  through study completion, an average 21months

Secondary Outcomes (6)

• Progression-Free Survival (PFS)

  through study completion, an average 21months

• Disease control rate (DCR)

  through study completion, an average 21months

• Duration of response (DOR)

  through study completion, an average 21months

• Time to progression (TTP)

  through study completion, an average 21months

• Overall survival (OS)

  every 12 weeks from the last dose of treatment for up to 1 year from the subject's last dose of study treatment

Study Arms (1)

irpagratinib

EXPERIMENTAL

Atezolizumab: 1200 mg on Day 1 of each 21-day cycle. Bevacizumab: 15 mg/kg on Day 1 of each 21-day cycle. ABSK-011 (irpagratinib): Patients will receive oral administration of ABSK-011 in a repetitive dosing regimen for a period of 21 consecutive days as a cycle, either once daily or twice daily, until the investigators make a comprehensive assessment of imaging examinations, laboratory data, and the clinical condition of the patients, and determine that there is intolerable toxicity or disease progression.

Drug: irpagratinib

Interventions

irpagratinib DRUG

Patients will receive oral administration of ABSK-011 capsules in a repetitive dosing regimen for a period of 21 consecutive days as a cycle, either once daily or twice daily, until the investigators make a comprehensive assessment of imaging examinations, laboratory data, and the clinical condition of the patients, and determine that there is intolerable toxicity or disease progression.

irpagratinib

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female, aged ≥19 at the time of signing inform consent form.
• 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.
• ECOG performance status score 0-1
• Life expectancy ≥ 3 months
• 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)
• 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
• \. 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.
• \. 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.
• \. Previous treatment with FGFR inhibitors including selective FGFR4 or pan-FGFR inhibitors.
• \. 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.
• \. 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.
• \. 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.
• \. 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.
• \. 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).
• \. 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).
• \. 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.
• \. 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
• \. Known fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma.
• \. Has a known active central nervous system (CNS) metastasis.

Sponsors & Collaborators

• Asan Medical Center: lead
• Abbisko Therapeutics Co, Ltd: collaborator

Study Sites (1)

Asan Medical Center,

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

Changhoon Yoo

CONTACT

82-2-3010-1727; cyoo.amc@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: June 8, 2025
• Study Start: March 16, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2029
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)