NCT07010497

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

A PHASE 2, OPEN-LABEL STUDY OF IRPAGRATINIB IN COMBINATION WITH ATEZOLIZUMAB AND BEVACIZUMAB IN PATIENTS WITH ADVANCED OR UNRESECTABLE HEPATOCELLULAR CARCINOMA (IAPETUS)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: Asan Medical Center · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Safety Run-in This part will enroll 9 patients administered with Irpagratinib orally 150 mg BID or 200 mg BID from study ABSK-011-101 in repeated 21-day cycles, plus Atezolizumab 1200 mg and Bevacizumab 15 mg/kg given IV Q3W. The tolerability will be evaluated upon the incidence of DLTs observed during Cycle 1. If DLT happened in ≤1 of the 3 DLT evaluable patients in 150 mg BID cohort, a combination regimen cohort with Irpagratinib orally 200 mg BID plus Atezolizumab 1200 mg Q3W+ Bevacizumab 15mg/kg Q3W will be initiated in additional 6 DLT evaluable patients to observe the incidence of DLTs. If DLT happened in ≤1 of the 6 patients in 200 mg BID, Irpagratinib 200 mg BID + Atezolizumab 1200 mg/Q3W + Bevacizumab 15mg/kg Q3W combination regimen will be recommended for the Expansion part. If DLT happened in ≥2 of the 6 DLT evaluable patients in 200 mg BID cohort and ≤1 of the 3 DLT evaluable patients in 150 mg BID, Irpagratinib 150 mg BID + Atezolizumab 1200 mg/Q3W + Bevacizumab 15mg/kg Q3W combination regimen will be recommended for the Expansion part. Subsequent patients of Safety Run-in should be dosed at least 7 days after the first patient's (sentinel patient) first dosing for each dose level of Irpagratinib. Eventually, the dose of Irpagratinib selected for the Expansion will be confirmed safe by at least 6 DLT evaluable patients in which ≤1 DLT event happen in 200 mg BID or at least 3 DLT evaluable patients in which ≤1 DLT event happen in 150 mg BID. Adverse events that meet the DLT definition occurring beyond the DLT observation period in patients will not be taken as a DLT but will be considered as a reference for the assessment of overall safety. Expansion Up to 24 eligible patients will be treated with Irpagratinib (the recommended dose from Safety Run-in) + Atezolizumab 1200 mg IV Q3W (dosed in 3-week cycles) and Bevacizumab 15 mg/kg IV Q3W (dosed in 3-week cycles). The decision for running stage two of the enrollment will be made after 3 responders observed in first evaluable 9 patients with FGF19 overexpression. Patients who interrupt or discontinue study treatments may continue the remaining treatment if the patients are experiencing clinical benefit in the opinion of the investigator and after consultation with the Investigator (e.g., patients who transiently withhold or permanently discontinue from treatment with one of the three drugs due to adverse events may continue with the remaining drug(s)).

Conditions

• Carcinoma, Hepatocellular

Interventions

Type	Name	Description
DRUG	irpagratinib	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.

Timeline

• Start date: 2026-03-16
• Primary completion: 2029-03-31
• Completion: 2029-03-31
• First posted: 2025-06-08
• Last updated: 2026-03-18

Locations

1 site across 1 country: South Korea