A Phase 2, Open-Label Study of ABSK-011 Combined Atezolizumab or SOC in HCC Patients

NCT05441475 | Enrolling By Invitation Phase 2

• 1 other identifier: ABSK-011-201
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open phase II clinical study, which consists of part a and Part B. Part a will evaluate the safety and tolerability of absk-011 combined with atilizumab in patients with advanced or unresectable HCC to And pk/pd characteristics, and determine the treatment plan of Part B. Part B will evaluate absk-011 combined with atilizumab Anti FGF19 overexpression in advanced stage or non resectable patients who have not received systemic therapy or only received first-line systemic therapy before In addition to the safety and tolerability of HCC subjects, the antitumor activity of the combination will be further evaluated. Part C comprises two parts: Part C1 and Part C2. A maximum of 54 subjects with advanced or unresectable hepatocellular carcinoma (HCC) with FGF19 overexpression and no prior systemic therapy will be planned for enrollment. Eligible subjects will be prioritized for assignment to Part C2 to receive study treatment. Treatment will continue until the earliest occurrence of intolerable toxicity, disease progression, initiation of new anti-tumor therapy, withdrawal of informed consent, loss to follow-up, death, or study termination.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (4)

• To evaluate the safety and tolerability of ABSK-011 combined with atezolizumab mab in subjects with advanced or unresectable HCC

  Incidence of dose limiting toxicity (DLT) in the first cycle；Incidence and grade of AE, SAE and AESI by CTCAE v5.0

  10 month

• To evaluate the objective response rate of ABSK-011 combined with atezolizumab in subjects with advanced FGF19 overexpression or unresectable HCC

  Objective response rate (ORR): complete response and partial response determined by the investigator according to RECIST v1.1 and to be confirmed

  10month

• To evaluate the safety and tolerability of ABSK-011 in combination with SOC in subjects with advanced or unresectable HCC, and to determine the dosing regimen for Stage 2 of Part C2.

  Incidence of dose limiting toxicity (DLT) in the first cycle；Incidence and grade of AE, SAE and AESI by CTCAE v5.0

  10month

• To evaluate the preliminary efficacy of ABSK-011 in combination with toripalimab and bevacizumab in subjects with FGF19-overexpressing advanced or unresectable HCC.

  ORR

  10month

Study Arms (3)

Part A&B ABSK-011 180 mg QD combined with atilizumab 1200 mg q3w.

EXPERIMENTAL

During part a, all subjects will receive continuous oral administration of absk-011 once a day (QD) or twice a day (bid) with an initial dose of 180 mg, and intravenous infusion (IV) of 1200 mg of atilizumab every 21 days (q3w). After the first subject (sentinel subject) in each dose cohort completed the first combined medication, follow-up subjects were administered at least 7 days later

Drug: ABSK-011 180 mg QD combined with atilizumab 1200 mg q3w

Part C1 ABSK-011 200mg BiD combined with atilizumab and bevacizumab.

EXPERIMENTAL

Part C1 is intended to enroll 6 subjects with advanced hepatocellular carcinoma (HCC) to receive ABSK-011 in combination with atezolizumab and bevacizumab.ABSK-011 will be administered orally at 200 mg twice daily (BID), with a single dose administered on Cycle 1 Day 1 (C1D1).

Drug: ABSK-011 200mg BID combined with atilizumab 1200 mg q3w and bevacizumab 15mg/kg

Part C2 ABSK-011 200mg BiD combined with toripalimab 240 mg + bevacizumab biosimilar 15 mg/kg

EXPERIMENTAL

Part C2 is planned to enroll a maximum of 48 subjects with advanced HCC, divided into two stages: Stage 1 of Part C2 intends to enroll 12 subjects with FGF19-overexpressing advanced HCC, who will be randomized 1:1 to two parallel treatment arms

Drug: ABSK-011 200mg BID combined with toripalimab 240 mg and bevacizumab biosimilar 15 mg/kg

Interventions

ABSK-011 180 mg QD combined with atilizumab 1200 mg q3w DRUG

During part a, all subjects will receive continuous oral administration of absk-011 once a day (QD) or twice a day (bid) with an initial dose of 180 mg, and intravenous infusion (IV) of 1200 mg of atilizumab every 21 days (q3w). After the first subject (sentinel subject) in each dose cohort completed the first combined medication, follow-up subjects were administered at least 7 days later

Also known as: Part A&B ABSK-011 180 mg QD combined with atilizumab 1200 mg q3w.

Part A&B ABSK-011 180 mg QD combined with atilizumab 1200 mg q3w.

ABSK-011 200mg BID combined with atilizumab 1200 mg q3w and bevacizumab 15mg/kg DRUG

Part C1 is intended to enroll 6 subjects with advanced hepatocellular carcinoma (HCC) to receive ABSK-011 in combination with atezolizumab and bevacizumab.ABSK-011 will be administered orally at 200 mg twice daily (BID), with a single dose administered on Cycle 1 Day 1 (C1D1).

Also known as: Part C1 ABSK-011 200mg BID combined with atilizumab 1200 mg q3w and bevacizumab 15mg/kg

Part C1 ABSK-011 200mg BiD combined with atilizumab and bevacizumab.

ABSK-011 200mg BID combined with toripalimab 240 mg and bevacizumab biosimilar 15 mg/kg DRUG

Part C2 is planned to enroll a maximum of 48 subjects with advanced HCC, divided into two stages: tage 1 of Part C2 intends to enroll 12 subjects with FGF19-overexpressing advanced HCC, who will be randomized 1:1 to two parallel treatment arms: Arm 1: ABSK-011 plus toripalimab plus bevacizumab biosimilar Arm 2: toripalimab plus bevacizumab biosimilar ABSK-011 will be administered orally at 200 mg BID, with a single dose administered on C1D1, and taken with food, preferably within 30 minutes after a meal. All intravenous agents will be administered on a Q3W schedule.Safety and tolerability evaluations will be performed for each treatment arm based on DLTs observed during Cycle 1 (21 days). Stage 2 of Part C2 is planned to enroll up to 36 subjects with FGF19-overexpressing advanced HCC, randomized 1:1 to Arm 1 or Arm 2, to further characterize the efficacy and safety profile of ABSK-011 in combination with standard of care (SOC).

Also known as: Part C2 ABSK-011 200mg BID combined with toripalimab 240 mg and bevacizumab biosimilar 15 mg/kg

Part C2 ABSK-011 200mg BiD combined with toripalimab 240 mg + bevacizumab biosimilar 15 mg/kg

Eligibility Criteria

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

You may qualify if:

• before implementing any program related procedures, the subjects should understand and voluntarily sign the written informed consent and indicate the date. Subjects should be able and willing to follow the study follow-up and study procedures in the protocol.
• there is no limit on gender, and the age when signing the informed consent is ≥ 18 years old.
• part a: subjects with advanced or unresectable HCC who must be confirmed by histology, cytology or imaging, are not suitable for curative surgery and / or local treatment, have disease progression or cannot tolerate standard treatment after standard treatment, and have no standard treatment due to physical conditions or disease status (according to local / regional guidelines), and the child Pugh score is 5-6.
• Part b: subjects with advanced or unresectable HCC who must be confirmed histologically or cytologically, are not suitable for curative surgery and / or local regional treatment, and have not previously received systematic treatment or only received first-line systematic treatment-
• Part C: Subjects with histologically or cytologically confirmed advanced or unresectable HCC who are not eligible for curative surgery and/or locoregional therapy and have not received prior systemic therapy, and who meet the following criteria:
• Provide archived tumor tissue samples or undergo biopsy for FGF19 overexpression testing at the central laboratory.
• BCLC stage B or C, Child-Pugh score 5-6, no hepatic encephalopathy, and no ascites requiring medical intervention within 7 days prior to the first dose.
• At least 1 measurable target lesion per RECIST 1.1. For subjects who received prior locoregional therapy (e.g., transarterial (chemo)embolization, radiofrequency ablation, percutaneous injection, cryoablation, high-intensity focused ultrasound, etc.), the target lesion must not have been treated with the above locoregional therapies, or the investigator has confirmed disease progression or absence of clinical benefit in the target lesion after prior locoregional therapy.
• Treatment with up to one cycle of a PD-1/PD-L1 inhibitor, with or without a VEGF inhibitor, prior to enrollment is permitted.

You may not qualify if:

• history of autoimmune diseases
• have a history of the second primary malignant tumor other than HCC within 5 years before screening,
• have a history of uncorrectable electrolyte disorders that affect serum potassium, calcium or phosphorus levels.
• meningeal metastasis or central nervous system (CNS) metastasis -

Sponsors & Collaborators

• Abbisko Therapeutics Co, Ltd: lead

Study Sites (1)

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

Hubei, Shanghai Municipality, 430030, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Bevacizumab; toripalimab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A+B, Single group, ABSK-011 combined with atelizumab in the treatment of patients with advanced or unresectable HCC; Part C1, Single group,is intended to enroll 6 subjects with advanced hepatocellular carcinoma (HCC) to receive ABSK-011 in combination with atezolizumab and bevacizumab.ABSK-011 will be administered orally at 200 mg twice daily (BID), with a single dose administered on Cycle 1 Day 1 (C1D1). Part C2 ,parallel, intends to enroll 48 subjects with FGF19-overexpressing advanced HCC, who will be randomized 1:1 to two parallel treatment arms.

Study Record Dates

• First Submitted: June 28, 2022
• First Posted: July 1, 2022
• Study Start: December 30, 2021
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)