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NCT04487067: AMETHISTA

A Study of Atezolizumab (Tecentriq) in Combination With Bevacizumab to Investigate Safety and Efficacy in Patients With Unresectable Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy-Amethista

Completed Phase 3 Results posted Last updated 22 September 2025
What this trial tests

Phase 3 trial testing Atezolizumab in Carcinoma, Hepatocellular in 152 participants. Completed in 13 August 2024.

Timeline
25 August 2020
Primary endpoint
13 August 2024
13 August 2024

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment152
Start date25 August 2020
Primary completion13 August 2024
Estimated completion13 August 2024
Sites21 locations across Italy

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Hepatocellular. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Grade 3-5 National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE V5) Bleeding/Haemorrhage Primary · Up to approximately 47.6 months

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Severity of AEs was graded using NCI CTCAE v5.0. Grade 3=Severe/medically significant but not immediately life-threatening, hospitalization/prolongation of hospitalization indicated; disa

Grade 3
GroupValue95% CI
Atezolizumab + Bevacizumab17
Grade 4
GroupValue95% CI
Atezolizumab + Bevacizumab3
Grade 5
GroupValue95% CI
Atezolizumab + Bevacizumab2
Overall Survival (OS) Secondary · Up to approximately 47.6 months

OS was defined as the time from initiation of study treatment to death from any cause. Kaplan-Meier (K-M) method was used to estimate the OS.

GroupValue95% CI
Atezolizumab + Bevacizumab20.7616.85 – 26.35
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Secondary · Up to approximately 47.6 months

An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs are defined as AEs with onset date on or after the start of the first study treatment component. Number of participants with any TEAEs are reported here.

GroupValue95% CI
Atezolizumab + Bevacizumab144
Progression-free Survival (PFS) Secondary · Up to approximately 47.6 months

PFS was defined as the time from initiation of study treatment to the first occurrence of disease progression (PD) or death from any cause (whichever occurs first), as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm). Participants alive and w

GroupValue95% CI
Atezolizumab + Bevacizumab8.807.89 – 11.24
Objective Response Rate (ORR) Secondary · Up to approximately 47.6 months

ORR was defined as the percentage of participants with complete or partial response (CR or PR), as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR.

GroupValue95% CI
Atezolizumab + Bevacizumab28.290.2173 – 0.3592
Time to Progression (TTP) Secondary · Up to approximately 47.6 months

TTP was defined as the time from initiation of study treatment to the first occurrence of PD, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. Participants without any PD were censored at the last assessment date. K-M method was used to estimate the TTP.

GroupValue95% CI
Atezolizumab + Bevacizumab11.248.48 – 15.77
Duration of Response (DOR) Secondary · Up to approximately 47.6 months

DOR was defined as the time from the first occurrence of a documented objective response (CR or PR) to PD or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at pri

GroupValue95% CI
Atezolizumab + Bevacizumab17.3513.54 – 27.24
Post-progression Survival (PPS) Secondary · Up to approximately 47.6 months

PPS was defined as the time from the first occurrence of PD as determined by the investigator according to RECIST v1.1 to death from any cause. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. Participants who were alive were censored at the last assessment date. K-M method was used to estimate the PPS.

GroupValue95% CI
Atezolizumab + Bevacizumab11.278.41 – 13.80
Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire Secondary · From Cycle 1 Day 1 to Cycle 63 Day 1 (1 Cycle = 21 days)

Participants self-reported symptomatic AEs using PRO-CTCAE, a validated item bank used to characterize presence, frequency of occurrence, severity, \&/or degree of interference with daily function of 78 patient-reportable symptomatic treatment toxicities. PRO-CTCAE contains questions that are rated either dichotomously (for determination of presence vs. absence) or on a 5-point Likert scale (for determination of frequency of occurrence,severity,\& interference with daily function). Treatment toxicities can occur with observable signs (e.g.,vomiting)/ non-observable symptoms (e.g.,nausea). A su

Cycle 1 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab39
Cycle 2 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab33
Cycle 3 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab23
Cycle 4 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab30
Cycle 5 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab23
Cycle 6 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab22
Cycle 7 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab17
Cycle 8 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab14
Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire Secondary · From Cycle 1 Day 1 to Cycle 63 Day 1 (1 Cycle = 21 days)

Participants self-reported symptomatic AEs using PRO-CTCAE, a validated item bank used to characterize presence, frequency of occurrence, severity, \&/or degree of interference with daily function of 78 patient-reportable symptomatic treatment toxicities. PRO-CTCAE contains questions that are rated either dichotomously (for determination of presence vs. absence) or on a 5-point Likert scale (for determination of frequency of occurrence,severity,\& interference with daily function). Treatment toxicities can occur with observable signs (e.g.,vomiting)/ non-observable symptoms (e.g.,nausea). A su

Cycle 1 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab15
Cycle 2 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab18
Cycle 3 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab12
Cycle 4 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab12
Cycle 5 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab10
Cycle 6 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab11
Cycle 7 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab7
Cycle 8 Day 1
GroupValue95% CI
Atezolizumab + Bevacizumab11

Adverse events — posted to ClinicalTrials.gov

Time frame: Other AEs: From initiation of study drug until 30 days after the final dose or initiation of new systemic anti-cancer therapy, whichever occurs first (up to approximately 47.6 months) SAEs, and All-cause mortality: From initiation of study drug until 90 days after the final dose or initiation of new systemic anti-cancer therapy, whichever occurs first (up to approximately 47.6 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Atezolizumab + Bevacizumab
Serious: 62/149 (42%)
Deaths: 102/149

Serious adverse events (74 terms)

ReactionSystemAtezolizumab + Bevacizumab
SepsisInfections and infestations
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Oesophageal varices haemorrhageGastrointestinal disorders
COVID-19Infections and infestations
AnaemiaBlood and lymphatic system disorders
AscitesGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
MelaenaGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
Biliary tract infectionInfections and infestations
PneumoniaInfections and infestations
EncephalopathyNervous system disorders
HeadacheNervous system disorders
Hepatic encephalopathyNervous system disorders
Transient ischaemic attackNervous system disorders
HaemorrhageVascular disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
Angina unstableCardiac disorders
BradycardiaCardiac disorders
Cardiac arrestCardiac disorders
Cardiac failureCardiac disorders
Myocardial infarctionCardiac disorders
DiplopiaEye disorders
Other adverse events (34 terms — click to expand)

ReactionSystemAtezolizumab + Bevacizumab
AstheniaGeneral disorders
HypertensionVascular disorders
DiarrhoeaGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
Decreased AppetiteMetabolism and nutrition disorders
PyrexiaGeneral disorders
ProteinuriaRenal and urinary disorders
FatigueGeneral disorders
Abdominal painGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
HypothyroidismEndocrine disorders
AscitesGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Back painMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
Blood bilirubin increasedInvestigations
COVID-19Infections and infestations
Oedema peripheralGeneral disorders
Platelet count decreasedInvestigations
Aspartate aminotransferase increasedInvestigations
Mucosal inflammationGeneral disorders
StomatitisGastrointestinal disorders
DysphoniaRespiratory, thoracic and mediastinal disorders
HypertransaminasaemiaHepatobiliary disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Alanine aminotransferase increasedInvestigations
HyperbilirubinaemiaHepatobiliary disorders

Most-reported serious reactions: Sepsis, Pulmonary embolism, Oesophageal varices haemorrhage, COVID-19, Anaemia, Ascites, Gastrointestinal haemorrhage, Melaena.

Data from ClinicalTrials.gov NCT04487067 adverse events section.

Sponsor's own description

This is a Phase IIIb, one arm, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab + bevacizumab in patients with unresectable HCC who have received no prior systemic treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  2. Hepatocellular carcinoma: signaling pathways and therapeutic advances.
    Zheng J, Wang S, Xia L, Sun Z, et al · · 2025 · cited 142× · PMID 39915447 · DOI 10.1038/s41392-024-02075-w
  3. Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets.
    Pessino G, Scotti C, Maggi M, Immuno-Hub Consortium. · · 2024 · cited 29× · PMID 38473265 · DOI 10.3390/cancers16050901
  4. Immunotherapy for hepatocellular carcinoma.
    Wang X, Lu J. · · 2024 · cited 22× · PMID 38855876 · DOI 10.1097/cm9.0000000000003060
  5. Emerging treatment modalities for systemic therapy in hepatocellular carcinoma.
    Qing X, Xu W, Zong J, Du X, et al · · 2021 · cited 17× · PMID 34419152 · DOI 10.1186/s40364-021-00319-3
  6. Combination of molecularly targeted therapies and immune checkpoint inhibitors in the new era of unresectable hepatocellular carcinoma treatment.
    Liu ZL, Liu JH, Staiculescu D, Chen J. · · 2021 · cited 17× · PMID 34104226 · DOI 10.1177/17588359211018026
  7. Atezolizumab plus bevacizumab as first-line treatment of unresectable hepatocellular carcinoma: interim analysis results from the phase IIIb AMETHISTA trial.
    Piscaglia F, Masi G, Martinelli E, Cabibbo G, et al · · 2025 · cited 13× · PMID 39874903 · DOI 10.1016/j.esmoop.2024.104110
  8. Atezolizumab and bevacizumab as first line therapy in advanced hepatocellular carcinoma: Practical considerations in routine clinical practice.
    Jain A, Chitturi S, Peters G, Yip D. · · 2021 · cited 11× · PMID 34630880 · DOI 10.4254/wjh.v13.i9.1132

Verify or expand the search:

Other trials of Atezolizumab

Trials testing the same drug.

Other recruiting trials for Carcinoma, Hepatocellular

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Trials by the same sponsor.

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