Today, we will be looking into the latest research and clinical trials focused on advanced hepatocellular carcinoma (HCC) in adults.

The following list has been carefully curated by evaluating the ongoing Phase 3 trials for HCC, specifically targeting adults in the United States. Please note that the dates provided are approximate and subject to change. This compilation primarily features studies that have released updates within the past 12 months.

This series aims to offer a glimpse into upcoming innovations in the field and how the outcomes of these studies could potentially influence clinical guidelines related to the topic.

Let’s take a dive into the Advanced HCC Clinical Trials!

Quick View Table of Advanced HCC Clinical Trials
Study TitlePhaseEnrollmentStart DateLast Update Posted
A Study of Nofazinlimab (CS1003) in Subjects With Advanced Hepatocellular CarcinomaPHASE 353412/13/20197/18/2024
A Study of Nivolumab in Combination With Ipilimumab in Participants With Advanced Hepatocellular CarcinomaPHASE 37329/30/20195/2/2024
Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer TherapyPhase 38376/10/20183/22/2024
Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Lenvatinib as First-line Therapy in Participants With Advanced Hepatocellular Carcinoma (MK-7902-002/E7080-G000-311/LEAP-002)PHASE 379412/31/20181/10/2024
Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular CarcinomaPHASE 3132410/11/20178/30/2024
A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152)PHASE 36509/14/20239/3/2024
Durvalumab and Tremelimumab as First Line Treatment in Participants With Advanced Hepatocellular CarcinomaPHASE 31106/27/20238/12/2024
Namodenoson in the Treatment of Advanced Hepatocellular Carcinoma in Patients With Child-Pugh Class B7 CirrhosisPHASE 34713/15/20237/31/2024
A Study to Evaluate SHR-1210 in Combination With Apatinib as First-Line Therapy in Patients with Advanced HCCPHASE 35436/10/20192/6/2024
A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular CarcinomaPHASE 35583/15/201810/23/2023
An Investigational Immuno-therapy Study of Nivolumab Compared to Sorafenib as a First Treatment in Patients With Advanced Hepatocellular CarcinomaPhase 374312/7/20153/19/2024

Phase 3 Advanced HCC Clinical Trials That are Active but not Recruiting:

A Study of Nofazinlimab (CS1003) in Subjects With Advanced Hepatocellular Carcinoma

Study Details | Source

  • Sponsor: CStone Pharmaceuticals
  • This is a multi-center, double-blind, randomized, phase III study to investigate the efficacy and safety of Nofazinlimab (CS1003) in combination with lenvatinib and placebo in combination with lenvatinib in the treatment of subjects with no prior systemic treatment and with unresectable advanced hepatocellular carcinoma (HCC). Subjects cannot be eligible for locoregional therapy. In this study, Nofazinlimab (CS1003) (or placebo) and lenvatinib are both considered as the study treatment while Nofazinlimab (CS1003) (or placebo) is the investigational product of and lenvatinib is selected as the basic treatment for HCC.
  • Interventions: DRUG: Nofazinlimab (CS1003)+Lenvatinib|DRUG: Nofazinlimab (CS1003) Placebo+Lenvatinib
  • Primary Outcomes Measures: Overall survival (OS), Expected to be 5.5 years after the first patient is enrolled.

A Study of Nivolumab in Combination With Ipilimumab in Participants With Advanced Hepatocellular Carcinoma

Study Details | Source

  • Sponsor: Bristol-Myers Squibb
  • The main purpose of this study is to compare the overall survival (OS) of nivolumab plus ipilimumab versus standard of care (SOC) (sorafenib or lenvatinib) in all randomized participants with advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy.
  • Interventions:DRUG: Nivolumab|DRUG: Ipilimumab|DRUG: Sorafenib|DRUG: lenvatinib
  • Primary Outcomes Measures: Overall Survival (OS), Up to 4 years

Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer Therapy

Study Details | Source

  • Sponsor: Exelixis
  • This Phase 3 study evaluates the safety and efficacy of cabozantinib in combination with atezolizumab versus the standard of care sorafenib in adults with advanced hepatocellular carcinoma (HCC) who have not received previous systemic anticancer therapy. A single agent cabozantinib arm will be enrolled in which subjects receive single agent cabozantinib in order to determine its contribution to the overall safety and efficacy of the combination with atezolizumab.
  • Interventions:DRUG: Cabozantinib|DRUG: Cabozantinib|DRUG: Sorafenib|DRUG: Atezolizumab
  • Primary Outcomes Measures: Duration of Progression Free Survival (PFS) for the experimental arm vs. the control arm, Duration of PFS per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST 1.1), Up to 27 months after the first subject is randomized. Defined as time from randomization to the earlier of progressive disease (PD) per RECIST 1.1 as determined by the Blinded Independent Radiology Committee (BIRC) or death from any cause. Duration of Overall Survival (OS) for the experimental arm vs. the control arm, up to 36 months after the first subject is randomized. Defined as time from randomization to date of death from any cause.

Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Lenvatinib as First-line Therapy in Participants With Advanced Hepatocellular Carcinoma (MK-7902-002/E7080-G000-311/LEAP-002)

Study Details | Source

  • Sponsor: Merck Sharp & Dohme LLC
  • “The purpose of this study is to evaluate the safety and efficacy of lenvatinib (E7080/MK-7902) in combination with pembrolizumab (MK-3745) versus lenvatinib in combination with placebo as first-line therapy for the treatment of advanced hepatocellular carcinoma in adult participants. The primary hypotheses of this study are that lenvatinib plus pembrolizumab is superior to lenvatinib plus placebo with respect to progression-free survival (PFS) and overall survival (OS).”
  • Interventions:DRUG: lenvatinib|BIOLOGICAL: pembrolizumab|DRUG: saline placebo
  • Primary Outcomes Measures: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), PFS was defined as the time from the date of the first documentation of disease progression, as determined by blinded independent central review (BICR) per RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeters \[mm\]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method., Up to approximately 41 months. Overall Survival (OS), OS was defined as the time from randomization until death from any cause, Up to approximately 41 months.

Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

Study Details | Source

  • Sponsor: AstraZeneca
  • This is a randomized, open-label, multi-center, global, Phase III study to assess the efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for unresectable HCC. The patients cannot be eligible for locoregional therapy
  • Interventions: DRUG: Durvalumab|DRUG: Tremelimumab (Regimen 1)|DRUG: Tremelimumab (Regimen 2)|DRUG: Sorafenib|DRUG: Durvalumab (Regimen 1)|DRUG: Durvalumab (Regimen 2)
  • Primary Outcomes Measures: Overall Survival (OS) – Treme 300 mg x1 Dose + Durva 1500 mg vs Sora 400 mg, OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This primary outcome measure presents OS analysis of Treme 300mg x1 dose + Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021)., From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).
Phase 3 Advanced HCC Clinical Trials That are Active and Recruiting 

A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152)

Study Details | Source

  • Sponsor: Hoffmann-La Roche
  • The purpose of this study is to assess the efficacy and safety of tiragolumab, an anti-TIGIT monoclonal antibody, when administered in combination with atezolizumab and bevacizumab as first-line treatment, in participants with unresectable, locally advanced or metastatic hepatocellular carcinoma (HCC).
  • Interventions: DRUG: Atezolizumab|DRUG: Bevacizumab|DRUG: Tiragolumab|OTHER: Placebo
  • Primary Outcomes Measures: Investigator-Assessed Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months)|Overall Survival (OS), From randomization to death from any cause (up to approximately 36 months).

Durvalumab and Tremelimumab as First Line Treatment in Participants With Advanced Hepatocellular Carcinoma (HCC)

Study Details | Source

  • Sponsor: AstraZeneca
  • This study will assess the safety and efficacy of Single Tremelimumab Regular Interval Durvalumab (STRIDE) as first-line therapy in participants with advanced unresectable HCC.
  • Interventions: DRUG: Durvalumab|DRUG: Tremelimumab
  • Primary Outcomes Measures: Incidence of grade 3 or 4 possibly related to treatment adverse events (PRAEs), PRAE is defined as an AE which has been assessed by the investigator to be possibly related to IMP., From the date of first dose of IMP until 6 months after the initiation of study intervention|Objective response rate (ORR), ORR is defined as the number (%) of participants with a confirmed objective tumour response (complete response [CR] or partial response [PR]) as determined by the investigator per Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1)., From the first dose of IMP until progression, or the last evaluable assessment in the absence of progression [approx. up to 33 months].

Namodenoson in the Treatment of Advanced Hepatocellular Carcinoma in Patients With Child-Pugh Class B7 Cirrhosis

Study Details | Source

  • Sponsor: Can-Fite BioPharma
  • This is a clinical trial in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh Class B7 (CPB7) cirrhosis whose disease has progressed on at least 1st-line therapy. The trial will evaluate the efficacy and safety of namodenoson as compared to placebo.
  • Interventions: DRUG: Namodenoson|DRUG: Placebo
  • Primary Outcomes Measures: Overall Survival (OS), Median duration of survival, From the time of randomization until the date of death from any cause, assessed up to 60 months.
Phase 3 Advanced HCC Clinical Trials That Have Been Completed

A Study to Evaluate SHR-1210 in Combination With Apatinib as First-Line Therapy in Patients With Advanced HCC

Study Details | Source

  • Sponsor: Jiangsu HengRui Medicine Co., Ltd.
  • This is a randomized, open-label, international, multi-center, phase III trial to evaluate the efficacy and safety of SHR-1210 plus apatinib mesylate versus sorafenib as first-line therapy in patients with advanced HCC.
  • Interventions: DRUG: SHR-1210|DRUG: Apatinib|DRUG: Sorafenib
  • Primary Outcomes Measures: Overall Survival (OS), OS was defined as the time from randomization to death from any cause., Up to approximately 3 years|Progression-free Survival (PFS) Evaluated by the Blinded Independent Review Committee (BIRC) Based on RECIST v1.1, PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) by tumor image evaluation or death from any cause whichever occurs first as determined by BIRC according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions and the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm), or a measurable increase in a non-target lesion, or the appearance of new lesions., Up to approximately 3 years.

A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma

Study Details | Source

  • Sponsor: Hoffmann-La Roche.
  • This study will evaluate the efficacy and safety of atezolizumab in combination with bevacizumab compared with sorafenib in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have received no prior systemic treatment.
  • Interventions: DRUG: Atezolizumab|DRUG: Bevacizumab|DRUG: Sorafenib
  • Primary Outcomes Measures: Overall Survival (OS) in the Global Population, OS was defined as the time from randomization to death from any cause., From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months)|Progression Free Survival by Independent Review Facility-Assessment (PFS-IRF) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the Global Population, PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm)., Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)|Overall Survival (OS) in the China Population, OS was defined as the time from randomization to death from any cause., From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months)|PFS-IRF Per RECIST v1.1 in the China Population, PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm)., Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months).

An Investigational Immuno-therapy Study of Nivolumab Compared to Sorafenib as a First Treatment in Patients With Advanced Hepatocellular Carcinoma

Study Details | Source

  • Sponsor: Bristol-Myers Squibb
  • The purpose of this study is to determine if nivolumab or sorafenib is more effective in the treatment of Advanced Hepatocellular Carcinoma.
  • Interventions: DRUG: Nivolumab|DRUG: Sorafenib
  • Primary Outcomes Measures: “Overall Survival (OS), OS is defined as the time from the date of randomization to the date of death due to any cause in all randomized participants. Participants who are alive will be censored at the last known alive dates. Based on Kaplan-Meier Estimates., time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months)”

Potential Guideline That May Be Affected Includes:

There you have it – a list of Phase 3 Clinical Trials for Advanced Hepatocellular Carcinoma as of September 2024. Stay tuned, for our next Guidelines+ Trials Rundown. Sign up for alerts and stay informed on the latest published guidelines and articles.


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