A Phase Ib/II Study of AK112 (PD-1/VEGF Bispecific Antibody) in Combination Therapy for Patients With Advanced Hepatocellular Carcinoma (HCC).
NCT Number: NCT06530251
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Hepatocellular Carcinoma
Interventions: DRUG: AK112|DRUG: Cadonilimab|DRUG: AK127|DRUG: AK130|DRUG: Sintilimab Injection|DRUG: Bevacizumab biosimilar
Sponsor: Akeso
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 280
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2028-09
Locations: Cancer Hospital Chinese Academy of Medical Sciences, Beijing, Beijing, China|Cancer Hospital of Shandong First Medical University (Shandong Cancer Institute,Shandong Cancer Hospital), Jinan, Shandong, China

Summary:
There're 2 parts in this interventional study:

1. The goal of phase Ib trial is to evaluate the safety and tolerability of AK112 in combination therapies for the purpose of observing the incidence of dose limit toxicity (DLT) as well as the confirmation of maximum tolerable dose (MTD) in the treatment of advanced hepatocellular carcinoma (HCC), so as to determine the recommended phase 2 dose (RP2D) in the second part of the trial.
2. The goal of phase II trial is to evaluate the safety and efficacy of AK112 in combination therapy or monotherapy in the treatment of HCC compared to the combination of Sintilimab and Bevacizumab analogues.

Primary Outcome Measures: Number of subjects with dose limiting toxicities (DLTs), DLTs will be assessed during the first three weeks of treatment. DLTs are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the DLT observation period., During the first three weeks.|Number of subjects with adverse events (AEs), AE refers to any untoward medical occurrence or deterioration of existing medical event after the subject signed the ICF, whether or not considered related to the study treatment., From the time of informed consent signed through 90 days after the last dose of study drug.|Objective Response Rate (ORR) (Phase II), ORR is defined as the proportion of subjects with BOR response of CR or PR (based on RECIST Version 1.1)., Up to approximately 2 years.
Secondary Outcome Measures: Objective Response Rate (ORR) (Phase Ib), ORR is defined as the proportion of subjects with BOR response of CR or PR (based on RECIST Version 1.1)., Up to approximately 2 years.|Objective Response Rate (ORR) Per mRECIST, ORR is defined as the proportion of subjects with BOR response of CR or PR (based on mRECIST)., Up to approximately 2 years.|Disease control rate (DCR), DCR is defined as the proportion of subjects with response of CR, PR and SD (based on RECIST Version 1.1)., Up to approximately 2 years.|Duration of Response (DoR), The time from first documented evidence of CR or PR until time of first documented disease progression., Up to approximately 2 years.|Progression Free Survival (PFS), PFS is defined as the interval between first dose and the earliest date of disease progression or death due to any cause., Up to approximately 2 years.|Time to response (TTR), Time between date of start of treatment until first documented response (CR or PR)., Up to approximately 2 years|Overall survival (OS), OS is defined as the time from first dose until death due to any cause, From baseline until death due to any cause.