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

ConditionCarcinoma, Hepatocellular

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age19+

SponsorAsan Medical Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

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.

Treatment groups

33 Participants

are divided into 1 treatment group

Group A: irpagratinibExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Incidence of DLTs

Safety Run-in: Incidence of DLTs in Cycle 1

Time frame

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

Time frame