A Study of AK112 in Patients With Advanced Hepatocellular Carcinoma (HCC)
ConditionHepatocellular Carcinoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorAkeso
About this trial
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 biosimilar.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Be able and willing to provide written informed consent.
Have a life expectancy of at least 3 months.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
HCC confirmed by histology/cytology or confirmed by the American Society for the Study of Hepatology (AASLD) clinical diagnostic criteria for hepatocellular carcinoma in patients with cirrhosis.
Disqualifiers
Components confirmed by histology/cytology, such as fibrous layer hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma.
Except for HCC, the subjects had other malignant tumors within the 5 years prior to enrollment. Subjects with other malignant tumors that have been cured through local treatment are not excluded, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast cancer in situ. If diagnosed with liver cancer or other malignant tumors more than 5 years before administration, pathological or cytological diagnosis of recurrent and metastatic lesions is required.
Tumor volume>50% liver volume; Portal vein cancer thrombus (Vp4), inferior vena cava cancer thrombus.
Tumors invade important organs and blood vessels around them, and researchers have determined that entering the study will cause a higher risk of bleeding.
Trial design
Design model
Parallel
Treatments tested in this trial
AK112
DrugFollowing a predefined dose and date.
Cadonilimab
DrugFollowing a predefined dose and date.
AK127
DrugFollowing a predefined dose and date.
AK130
DrugFollowing a predefined dose and date.
Sintilimab Injection
DrugFollowing the local label direction.
Bevacizumab biosimilar
DrugFollowing the local label direction.
Treatment groups
280 Participants
are divided into 5 treatment groupsGroup A: AK112 in combination with AK130Experimental treatment 2 interventions
Group B: AK112 in combination with AK127Experimental treatment 2 interventions
Group C: AK112 in combination with CadonilimabExperimental treatment 2 interventions
Group D: AK112Experimental treatment 1 intervention
Group E: Sintilimab in combination with Bevacizumab biosimilarActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
During the first three weeks.2
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.
Time frame
From the time of informed consent signed through 90 days after the last dose of study drug.3
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).
Time frame
Up to approximately 2 years.Secondary outcomes
1
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).
Time frame
Up to approximately 2 years.2
Objective Response Rate (ORR) Per mRECIST
ORR is defined as the proportion of subjects with BOR response of CR or PR (based on mRECIST).
Time frame
Up to approximately 2 years.3
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).
Time frame
Up to approximately 2 years.4
Duration of Response (DoR)
The time from first documented evidence of CR or PR until time of first documented disease progression.
Time frame
Up to approximately 2 years. Source ClinicalTrials.gov