NCT05440864Phase 2Recruiting
University Health Network, Toronto · University Health Network, Toronto, Ontario
Hepatocellular Carcinoma (HCC) is the third most common cause of death from cancer world wide and the incidence is rising globally. Despite surgical resection in appropriate patients, many patients recur.
The results of the IMbrave150 study have established PD-L1 inhibition in combination with VEGF inhibition as a new standard of care highlighting the role of immune checkpoint inhibition in advanced HCC. In addition, the combination of Tremelimumab and Durvalumab has demonstrated efficacy in advanced HCC; the HIMALAYA trial has now completed accrual in treatment naïve patients with advanced HCC. Furthermore the earlier use of immune checkpoint inhibitors in this disease are being explored with adjuvant combination strategies, including the EMERALD-2 trial (NCT03847428). Neoadjuvant treatment in HCC allows for delivery of treatment pre surgery and may enhance pathological responses and improve outcomes. The delivery of combination CTLA-4 and PD-L1 inhibition has demonstrated efficacy in other tumour types in the neoadjuvant setting where the impact on the tumour microenvironment has also been evaluated. The safety and feasibility of Durvalumab and Tremelimumab in resectable HCC has yet to be established.
Hypotheses Pre-operative (pre-op) Durvalumab and Tremelimumab treatment is safe and feasible in pre surgical setting for upfront resectable HCC The combination of Durvalumab and Tremelimumab pre-op will result in changes in immune and molecular characteristics within the tumour microenvironment.
Overall Study Design This is a phase II, open-label multi-centre study to assess safety of Durvalumab and Tremelimumab treatment in pre-op setting for upfront resectable HCC, followed by adjuvant Durvalumab.
28 patients are expected to enrol at three sites. Patients will receive pre-op: 1 dose Tremelimumab (300mg) (T300) with Durvalumab (1500mg) at cycle 1 and 1 further cycle of Durvalumab (1500mg) only. Post-surgical resection, adjuvant therapy will consist of Durvalumab Q4W for up to a maximum of 12 months in total or 13 cycles of Durvalumab (11 cycles post op).
All participants will be treated until progressive disease or unacceptable toxicity or withdrawal of consent or another discontinuation criterion is met. All participants will be followed for survival until the end of study.
No dose reductions of Tremelimumab and Durvalumab will be allowed. Statistics The primary objective of this study is to assess safety of pre-op treatment with Durvalumab and Tremelimumab.
For safety, with the null proportion of patients who discontinue treatment due to AEs, imAEs or SAE is 30% versus the alternative proportion is 10% or less than 10%, a sample size of 28 provides 80% power to detect the proportion difference with a two-sided alpha level of 0.1.
The sample size estimate is based on the two-sided exact test for binomial proportion considering Binomial Enumeration method.
Eligibility: 18 Years to · All · For inclusion in the study, patients should fulfil the following criteria at time of study enrolment or when indicated:
1. Patient must be capable of providing written informed consent.
2. Age \>18 years at time of study entry
3. Histologically proven resectable HCC (early and intermediate stage HCC)\*
4. Must consent to provide biopsy sample prior to treatment
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
6. Childs Pugh score of 5 or 6
7. ALBI grade 1†
8. Patients with HBV infection, which is characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV DNA (≥10 IU/ml or above the limit of detection per local lab standard), must be treated with antiviral therapy, as per institutional practice, to ensure adequate viral suppression (HBV DNA ≤2000 IU/mL) prior to study entry. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (\<10 IU/ml or under limit of detection per local lab standard) do not require anti-viral therapy prior to study entry. These subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥10 IU/ml or above the limit of detection per local lab standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication.
9. Patients with HCV infection must have management of this disease per local institutional practice throughout the study. HCV diagnosis is characterized by the presence of detectable HCV ribonucleic acid (RNA) or anti-HCV antibody upon enrollment.
10. Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients.
11. Female of childbearing potential and non-sterilized male partners of a female patient of childbearing potential must agree to use effective method of contraception from the time of screening throughout the total duration of the drug treatment and 6 months after the last dose of study treatment. (See exclusion #22 for definition of effective method of contraception).
12. Adequate normal organ and marrow function as defined below within screening period:
* Haemoglobin ≥9.0 g/dL
* Absolute neutrophil count (ANC ≥1.0 × 109 /L)
* Platelet count ≥65 × 109/L
* Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). \<\<This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
* AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal
* Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine clearance CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
Males:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x serum creatinine (mg/dL)
Females:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 / 72 x serum creatinine (mg/dL)
\- Albumin ≥2.8g/dl
\- International normalized ratio ≤1. (for patients receiving Warfarin, please consult with the study physician)
13. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
14. Body weight \> 30kg
NCT07303712Phase IIRecruiting
Palo Alto Veterans Institute for Research · VA Palo Alto Health Care System, Palo Alto, California
The purpose of this study is to determine if baseline liquid biopsy assays (CTC and cf-DNA) as well as single circulating tumor cell-DNA (sCTC DNA) dynamics in the early post-treatment period can predict subsequent treatment response to Y-90 radioembolization in patients with hepatocellular carcinoma (HCC).
Eligibility: 18 Years to · All · 1. Age \> or = 18 years
2. HCC confirmed on imaging, BCLC stage 0, A, B, or C
3. Transarterial Y90 radioembolization approved by multidisciplinary tumor board -
NCT05248581Phase IIRecruiting
University of Rochester · University of Rochester Medical Center, Rochester, New York
The goal of this study is to create a data registry to capture clinical, pathologic, and molecular data/outcomes for patients with metastatic colorectal cancer who undergo live donor liver transplantation.
Eligibility: 18 Years to · All · * Age ≥ 18
* Non-amenable to curative hepatic resection as defined by FLR \<30%
* Histologically confirmed adenocarcinoma of the colon or rectum
* Candidate for LDLT for colorectal liver metastasis per the University of Rochester liver transplant program
NCT06426992NARecruiting
Seoul National University Hospital · Seoul National University Hospital, Seoul
The purpose of this study is to determine the technical success rate of creating a safety margin of 5 mm or more including the tumor by performing image-guided percutaneous microwave thermal therapy using a microwave generator and antenna developed by StarMed for the treatment of small liver cancer and the 1-year local recurrence rate based on follow-up imaging tests.
Eligibility: 20 Years to 85 Years · All · * Child-Pugh Class A or B
* Patients with suspected hepatocellular carcinoma or residual/recurrent hepatocellular carcinoma of 4 cm or less on MDCT, CEUS, or MRI performed within the last 60 days or Patients with suspected metastatic liver cancer of 4 cm or less on MDCT, CEUS, or MRI performed within the last 60 days, for whom microwave thermal ablation is being considered
NCT06898398Phase IIRecruiting
Sun Yat-sen University · Chinese PLA general hospital, Beijing, Beijing Municipality
Huge hepatocellular carcinoma (HCC) is defined as a tumor with a maximum diameter greater than 10 cm. With advancements in surgical techniques, hepatectomy can be performed safely in some patients with huge HCC without vascular invasion or distant metastasis and with preserved liver function. The high risk of recurrence after surgery is another challenge for surgeons. Neoadjuvant TACE has been shown to improve the clinical outcomes of patients with HCC, especially those with a high risk of recurrence, such as those with multinodular tumors, large tumors, and tumor thrombus. The present multicenter study aimed to evaluate the efficacy of neoadjuvant TACE in patients with huge HCC who underwent liver resection.
Eligibility: 18 Years to 75 Years · All · 1. clinical or pathological diagnosis of primary HCC;
2. tumor diameter \> 10 cm on images before inclusion;
3. age 18 to 75 years;
4. no macrovascular invasion or extrahepatic metastasis;
5. liver resection with complete removal of the tumor and adequate remnant liver volume;
6. albumin-bilirubin (ALBI) grade I and II;
7. Eastern Cooperative Oncology Group performance status (ECOG) score of 0-1;
8. hemoglobin level ≥ 8.5 g/dL, total bilirubin level ≤ 30 mmol/L, alanine transaminase (ALT) and aspartate aminotransferase (AST) levels ≤ 5 × upper limit of normal, serum creatinine level ≤ 1.5 × upper limit of normal;
9. prothrombin time ≤ 18 s or international normalized ratio \< 1.7.
NCT05185739Phase 2Recruiting
University College, London · Queen Elizabeth Hospital, Birmingham
This is a multicentre randomised 3-arm phase II clinical trial in patients with resectable Hepatocellular Carcinoma (HCC). Sixty patients will be randomized 1:1:1 to 6 weeks of pre-operative therapy with: pembrolizumab, lenvatinib or the combination of pembrolizumab and lenvatinib followed by up to 12 months treatment with post-operative pembrolizumab. The aim of the study is to compare the efficacy of pembrolizumab combined with lenvatinib with that of pembrolizumab and lenvatinib alone in terms of major pathological response in patients with resectable HCC. Major pathological response will be defined by the proportion of patients with less than 10% viable tumour at resection.
Eligibility: 18 Years to · All · 1. Have a diagnosis of Hepatocellular Carcinoma (HCC) confirmed by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) and suitable for surgical resection. Radiological confirmation of diagnosis is provided by the study site and defined by the presence of a liver mass of at least 1 cm and exhibiting arterial hypervascularity with washout in the portal venous phase seen in a tri-phasic magnetic resonance imaging (MRI).
2. Measurable disease based on RECIST 1.1
3. HCC amenable to R0 resection with curable intent
4. Child-Pugh A liver disease
5. International normalised ratio (INR) ≤1.4
6. ECOG Performance status 0 or 1
7. Adequate haematological function as defined by:
* Haemoglobin (Hb) \> 90g/l
* Neutrophil Count \> 1.5 x 109/l
* Platelets \> 75 x 109/l
8. Adequate renal function with GFR \>40ml/min using a validated creatinine clearance calculation (e.g. Cockcroft-Gault or Wright formula)
9. Adequate liver function as defined by:
* Aminotransferase (ALT) or aspartate aminotransferase (AST) \< 5.0 x ULN
* Albumin \>32g/l
* Amylase ≤ 1.5 x ULN
10. Patients with past or ongoing hepatitis C virus (HCV) infection will be eligible for the study if HCV viral load is undetectable at screening. The treated patients must have completed their treatment curative anti-viral treatment at least 4 weeks prior to randomisation.
11. Patients with controlled hepatitis B will be eligible as long as they meet the following criteria:
* Antiviral therapy for hepatitis B virus (HBV) must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL prior to randomisation. Patients on active HBV therapy with viral loads under 500 IU/mL should stay on the same therapy throughout study treatment.
* Patients who are positive for anti-hepatitis B core antibody (HBc), negative for hepatitis B surface antigen (HBsAg), and negative or positive for anti-hepatitis B surface antibody (HBs), and who have an HBV viral load under 500 IU/mL, do not require HBV anti-viral prophylaxis
12. 18 years of age or over
13. Predicted life expectancy of \> 3 months
14. Patients must have given written informed consent
15. Patients must have the ability to swallow oral medication
16. Must be willing to use effective contraception during study for 120 days after last dose.
NCT05935189Phase IIRecruiting
Nikomed Medical Center · Nikomed Medical Center, Yerevan
The goal of the study is to establish a cancer registry to facilitate research and assist in the identification of additional risk factors for hepatocellular carcinoma. The main objectives are:
1. provide a mechanism to store the information about subjects with hepatocellular carcinoma
2. use of tissue samples for translational/further research purposes
Eligibility: 18 Years and older · All · * Patients with biopsy-confirmed diagnosis of HCC
* Armenian descent
* Having given their signed Informed consent
NCT07331883Phase 2Recruiting
Ruijin Hospital · Sanming First Hospital, Sanming, Fujian
Primary liver cancer-particularly hepatocellular carcinoma (HCC)-remains a major health burden in China, characterized by high incidence and mortality rates and poor 5-year survival. Spontaneous rupture of HCC (SRHCC), although a relatively uncommon complication, is associated with extremely high mortality and marked geographic variation, with disproportionately higher incidence and rupture-related deaths reported in Asian populations. For patients with preserved liver function and resectable tumors, hepatic resection can offer favorable long-term survival and even a potential cure. However, despite surgical removal, the risk of postoperative recurrence is substantially increased, and long-term outcomes remain unsatisfactory. Currently, there is no validated adjuvant therapy to reduce recurrence or improve survival after resection.
In recent years, immune checkpoint inhibitors (ICIs) in combination with anti-angiogenic agents have demonstrated synergistic antitumor activity and manageable safety in advanced HCC. Notably, studies of sintilimab plus a bevacizumab biosimilar have shown significant improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Moreover, emerging evidence in the adjuvant and perioperative settings suggests that PD-1 blockade may delay recurrence in high-risk patients, such as those with microvascular invasion.
Based on the high postoperative recurrence rate in SRHCC patients and the existing therapeutic gap, along with established evidence of the efficacy of immune checkpoint inhibitors combined with antiangiogenic therapy in advanced HCC, conducting a prospective Phase II single-arm study of adjuvant therapy with sintilimab plus the bevacizumab biosimilar holds significant clinical and scientific value. This study aims to evaluate the tolerability of this combination regimen in postoperative SRHCC patients at high risk of recurrence. It is expected to provide a more effective treatment option for patients diagnosed with spontaneously ruptured hepatocellular carcinoma, improve their prognosis, and offer scientific evidence for future treatment strategies.
Eligibility: 18 Years to 75 Years · All · * Patients voluntarily provide written informed consent, with authorization obtained from the patient or legal representative prior to any protocol-related procedures.
* Age ≥ 18 years and ≤ 75 years; both female and male
* Spontaneous tumor rupture with hemorrhage confirmed by imaging prior to or during surgery, with a postoperative pathological diagnosis of hepatocellular carcinoma (HCC).
a) For cases where tumor rupture is an incidental finding during surgery, a clinical history of abdominal pain within the two weeks preceding surgery is required.
* CNLC Stage I-II.
* Having undergone curative surgical resection, with intraoperative irrigation using ≥5000 mL of distilled water or normal saline, confirmed negative surgical margins on postoperative pathology, and achieving a complete response (CR) confirmed by imaging within 4-8 weeks after surgery.
* ECOG PS 0-1
* Child-Pugh A (score ≤6).
* Life expectancy ≥12 months
* Laboratory test results obtained within 3 days prior to the first dose must meet the following criteria:
1. Hematological:(Except for hemoglobin, the patient must not have received a blood transfusion, granulocyte colony-stimulating factor \[G-CSF\], or hematopoietic agents within 2 weeks prior to screening.) i. Absolute neutrophil count ≥1.5 × 10⁹/L; ii. Platelet count ≥75 × 10⁹/L; iii. Hemoglobin ≥90 g/L.
2. Serum biochemistry:
i. Serum albumin ≥30 g/L; ii. Total bilirubin ≤1.5 × ULN; iii. ALT and AST ≤3 × ULN; iv. Serum creatinine ≤1.5 × ULN, or creatinine clearance \>50 mL/min.
3. International normalized ratio (INR) ≤1.2 or prothrombin time (PT) ≤2 seconds above the upper limit of normal.
4. Urinalysis:Urine protein \<2+.(If urine protein is ≥2+, a 24-hour urine protein test may be performed; patients may be enrolled if 24-hour urine protein \<1.0 g.)
* For patients with HBV infection (i.e., HBsAg-positive), HBV DNA must be tested. HBV DNA levels must be \<2000 IU/mL (or \<10⁴ copies/mL if the study site reports results in copies/mL). Patients with HBV DNA ≥2000 IU/mL must receive at least 1 week of antiviral therapy prior to the first dose, using only nucleos(t)ide analogues such as entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide. HBV DNA levels must show a ≥1-log (10-fold) reduction before initiation of study treatment. All HBV-infected patients must continue antiviral therapy throughout the entire study period. Patients who are HCV RNA-positive must receive antiviral treatment according to current clinical guidelines.
* Female patients of childbearing potential must have a negative β-hCG pregnancy test prior to the first dose. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use effective contraception during treatment and for 6 months after the last dose of study medication.
NCT04657042Phase IIRecruiting
University of Virginia · University of Virginia, Charlottesville, Virginia
The purpose of this study is to develop new ways to make medical images of the lungs and liver of adults using a technique called four-dimensional magnetic resonance imaging (4D-MRI). This technique produces three-dimensional movies of the inside of the chest and abdomen while the patient is breathing. (The fourth dimension is time!)
This new way of medical imaging is being developed to help cancer patients undergoing radiation therapy. Radiation therapy is used to treat cancerous tumors. For radiation therapy to be effective, the precise size, shape, and location of the tumor within the body must be known. A particular difficulty for radiation treatment of lung and liver cancer is that the tumor moves during treatment because the patient is breathing. Therefore, tumor motion must also be incorporated into the treatment plan. This study aims to improve radiation treatment planning through better targeting and dose estimation based on 4D-MRI. Before this new imaging method can be used for radiation treatment planning, it must be tested in living, breathing volunteers.
Eligibility: 18 Years to 82 Years · All · The inclusion criteria for lung and liver cancer patients are:
* Patient is 21 or older
* Patient has primary or metastatic tumor(s) in the lungs or the liver
* Diameter of the tumor(s) is less than 7 cm
* Patient will receive radiation therapy (ordered by the treating Radiation Oncologist) as part of their treatment regimen
* Patient will undergo a planning CT scan with tumor motion assessment (planning 4D-CT ordered by the treating Radiation Oncologist) as part of their treatment regimen
* Patient has signed informed consent and is willing to comply with the 4D-MRI imaging protocol
The inclusion criteria for healthy volunteers are:
* Subject is 18 or older
* Subject has signed informed consent and is willing to comply with the 4D-MRI imaging protocol
NCT05185245NARecruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna · IRCCS Azienda Ospedaliero - Universitaria di Bologna, Bologna
The study aims to evaluate the efficacy of liver transplantation in the context of non-resectable colorectal liver metastasis. The primary endpoint is the overall survival in this group of patients while the secondary endpoint is the disease-free survival.
Patients included in this protocol will be evaluated either for whole or partial liver transplantation from deceased or living donors.
Type of different transplantations proposed are as follows:
1. Whole liver graft or partial liver (split) from a deceased donor
2. Partial liver graft retrieved from a deceased donor and orthotopically implanted after having performed a left hepatectomy in the recipient.
3. Partial liver graft retrieved from a deceased donor and heterotopically implanted if total hepatectomy can not be performed.
4. Partial liver graft retrieved from a living donor and orthotopically implanted after having performed total hepatectomy.
5. Partial liver graft retrieved from a living donor and orthotopically implanted after having after having performed a left hepatectomy in the recipient.
6. Partial liver graft retrieved from a living donor and heterotopically implanted if total hepatectomy can not be performed.
In cases 2-3-5-6 total hepatectomy of native liver can be secondarily performed after having achieved a proper graft hypertrophy in order to avoid a small for size syndrome
Eligibility: 18 Years to 73 Years · All · * Primary tumor resected according to standard oncological practice, p≤T4a, R0 resection
* Colorectal liver metastasis considered as non-resectable either up-front or after previous hepatic resections
* No local recurrence of primary colon cancer confirmed by Positron Emission Tomography, Computed Tomography and colonoscopy
* No extra-hepatic metastatic disease confirmed by Positron Emission Tomography and Computed Tomography
* Good performance status Eastern Cooperative Oncology Group 0 or 1
* Neutrophils \> 1.000
* Patients who received at least one line of chemotherapy for at least 3 months with partial response or stable disease according to modified Response Evaluation Criteria in Solid Tumours
* Carcino-Embryonic Antigen \< 80 µg/L or reduction of ≥ 50% of highest Carcino-Embryonic Antigen level observed
* Written informed consent
* No other contraindications to liver transplantation
NCT06689670NARecruiting
inTumo Therapeutics, Inc. · Koc University Hospital, Topkapı, Istanbul
The goal of this clinical trial is to learn if INT001 can ablate liver tumors in adults in an outpatient setting. It will also help us learn about the safety of INT001. The main questions it aims to answer are:
1. Using a needle under image guidance, the liver tumor is accessed and INT001 is injected. Upon injection into tumor, does INT001 ablate/kill the tumor entirely?
2. What medical problems do participants experience when receiving INT001?
Participants will:
Receive INT001 on day 1. Visit the clinic day 7, 30 and 90. Receive lab tests during each visit and MRI on day 30 and 90.
Eligibility: 18 Years to 100 Years · All · 1. Diagnosis of primary or secondary liver cancer.
2. ECOG Performance Status score of 0 - 2
3. Age ≥18 years, \<100 years
4. Life expectancy of ≥3 months
5. Patient is unsuitable for surgical resection or transplantation
6. Ability of the patient to understand and sign the Informed Consent Form describing the study's nature
7. Volunteer's willingness and ability to comply with protocol requirements, including all procedures, clinical evaluations, and follow-up visits
NCT05844046Phase 2Recruiting
Enrico De Toni · Hospital of the University of Munich, Munich
This is a randomized, open-label, multi-center, international, Phase II study to assess the efficacy and safety of sequential or up-front triple treatment with durvalumab, tremelimumab and bevacizumab for non-resectable hepatocellular carcinoma.
Patients will be randomized in a 1:1 ratio to one of the following arms:
Arm A: initial treatment with durvalumab plus tremelimumab followed by treatment escalation with the addition of bevacizumab upon radiological progression or in the absence of objective response
Arm B: up-front treatment with durvalumab, tremelimumab and bevacizumab
Patients will be stratified according to macrovascular invasion and etiology of liver disease (viral etiologies versus others).
Eligibility: 18 Years to · All · KEY INCLUSION CRITERIA
Age ≥18 years at the time of study entry
Confirmed HCC based on histopathological findings from tumor tissues.
Must not have received prior systemic therapy for HCC.
Not eligible for locoregional therapy for unresectable HCC. For patients who progressed after locoregional therapy for HCC, locoregional therapy must have been completed ≥28 days prior to the baseline scan for the current study.
Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C
Child-Pugh Score class A
ECOG performance status of 0 or 1 at enrollment
At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. A lesion which progressed after previous ablation or TACE could be measurable if it meets these criteria.
Adequate organ and marrow function
KEY EXCLUSION CRITERIA
Previous study drug(s) assignment in the present study.
Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 28 days of the first dose of study drug(s).
Major surgical procedure or significant traumatic injury within 28 days prior to the first dose of study drug(s), abdominal surgery, abdominal interventions, or significant abdominal traumatic injury within 60 days prior to randomization
History of allogeneic organ transplantation (eg, liver transplant).
History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy
Clinically meaningful ascites
Patients with main portal vein thrombosis (i.e., thrombosis in the main trunk of the portal vein, with or without blood flow) on baseline imaging.
Patient currently exhibits symptomatic or uncontrolled hypertension
Active or prior documented autoimmune or inflammatory disorders, diverticulitis. Patients without active disease in the last 5 years are excluded unless discussed with the Study Physician and considered appropriate for study participation.
Patients co-infected with HBV and HCV, or co-infected with HBV and hepatitis D virus (HDV).
History of another primary malignancy except for the exceptions defined by the study protocol.
Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart).
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
History of active primary immunodeficiency.
Receipt of live attenuated vaccine within 30 days prior to the first dose of study drug(s). Note: Patients, if enrolled, should not receive live vaccine while receiving study drug(s) and up to 30 days after the last dose of study drug(s).
Major gastrointestinal bleeding within 4 weeks prior to randomization.
Patients with untreated or incompletely treated varices with bleeding or high-risk for bleeding. Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD within 6 months prior to randomization do not need to repeat the procedure. Those who have received banding and/or sclerotherapy and with no bleeding event within the prior 6 months are eligible provided that a re-endoscopy is performed and that varices remained obliterated, minimal or Grade I
Significant vascular disease including aortic aneurysm requiring surgical repair or peripheral arterial thrombosis with 6 months prior to randomization
History of abdominal or tracheoesophageal fistula or gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization.
Evidence of bleeding diathesis or significant coagulopathy
Severe, nonhe
