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NCT04732286

A Study of Atezolizumab in Combination With Bevacizumab in Spanish Patients With Unresectable or Unsuitable for Locoregional Treatments Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy

Terminated Phase 3 Results posted Last updated 8 May 2025
What this trial tests

Phase 3 trial testing Atezolizumab in Carcinoma, Hepatocellular in 100 participants. Terminated before completion.

Timeline
4 May 2021
Primary endpoint
26 April 2024
26 April 2024

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment100
Start date4 May 2021
Primary completion26 April 2024
Estimated completion26 April 2024
Sites25 locations across Spain

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 Who Discontinued Atezolizumab and/or Bevacizumab Due to Adverse Events (AE) of Grade ≥ 3 Primary · From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months)

AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavourable 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. The severity of AEs was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) with the following grades: Grade 1 = asymptomatic or mild symptom

GroupValue95% CI
Atezolizumab + Bevacizumab19
Overall Survival (OS) Secondary · Up to 35 months

OS was defined as the time from initiation of study treatment to death from any cause. OS was analyzed using Kaplan-Meier (K-M) methods and Greenwood's formula. Any participant who did not die during the study was censored at the last known date to be alive.

GroupValue95% CI
Atezolizumab + Bevacizumab24.818.55 – NA
Progression-free Survival (PFS) Secondary · Up to 35 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 Tumours 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). PFS was analyzed using K

GroupValue95% CI
Atezolizumab + Bevacizumab9.37.01 – 12.40
Objective Response Rate (ORR) Secondary · Up to 35 months

ORR = percentage of participants with a complete or partial response (CR or PR), on 2 consecutive investigator assessments ≥ 4 weeks apart in participants with measurable disease at baseline as determined by the investigator according to RECIST v1.1. CR = disappearance of all target lesions and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR = at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants without a post-baseline tumor assessment were considered non-responders. 95% confidence in

GroupValue95% CI
Atezolizumab + Bevacizumab24.216.9 – 33.5
Time to Progression (TTP) Secondary · Up to 35 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%, SOD must also demonstrate an absolute increase of ≥ 5 mm. TTP was analyzed using K-M methods and Greenwood's formula. Any participant who had no disease progression was censored at the last known date without disease progression.

GroupValue95% CI
Atezolizumab + Bevacizumab11.28.30 – 13.59
Duration of Response (DOR) Secondary · Up to 35 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 and any pathological lymph nodes must have a 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

GroupValue95% CI
Atezolizumab + Bevacizumab15.97.87 – 23.74
Percentage of Participants Who Started Second-line Treatment Secondary · Up to 35 months

Participants who started second-line of treatment were assessed. Percentages have been rounded off.

GroupValue95% CI
Atezolizumab + Bevacizumab24.2
Change From Baseline in International Normalized Ratio (INR) Secondary · Baseline up to Cycle 42 (1 cycle = 21 days)

The INR is a standardized measure of the prothrombin time. Blood samples were collected from participants to evaluate coagulation parameters.

Baseline
GroupValue95% CI
Atezolizumab + Bevacizumab1.1± 0.1
Cycle 42
GroupValue95% CI
Atezolizumab + Bevacizumab0.1± 0.0
Change From Baseline in Albumin-Bilirubin (ALBI) Score Secondary · Baseline up to Cycle 42 (1 cycle = 21 days)

Blood samples were collected from participants to evaluate of ALBI grades. ALBI assessment grades of 1 to 3 was based on ALBI score calculation. ALBI score= log10 bilirubin (micromole per liter) \[μmol/L\] × 0.66 + albumin (grams per liter) \[g/L\] × -0.0852. ALBI score ≤ -2.60 = ALBI grade 1; -2.60 \< ALBI score ≤ -1.39 = ALBI grade 2 and -1.39 \< ALBI score = ALBI grade 3.

Baseline
GroupValue95% CI
Atezolizumab + Bevacizumab-2.7± 0.4
Cycle 42
GroupValue95% CI
Atezolizumab + Bevacizumab0.4± 0.4
Percentage of Participants With Ascites and/or Hepatic Encephalopathy Secondary · Up to approximately 32 months

Deterioration of hepatic function was monitored by presence of ascites and/or hepatic encephalopathy.

GroupValue95% CI
Atezolizumab + Bevacizumab17

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Atezolizumab + Bevacizumab:
Serious: 46/100 (46%)
Deaths: 51/100

Serious adverse events (64 terms)

ReactionSystemAtezolizumab + Bevacizumab:
Hepatic EncephalopathyNervous system disorders
Oesophageal Varices HaemorrhageGastrointestinal disorders
AscitesGastrointestinal disorders
Back PainMusculoskeletal and connective tissue disorders
HepatitisHepatobiliary disorders
PyrexiaGeneral disorders
Abdominal PainGastrointestinal disorders
Gastrointestinal HaemorrhageGastrointestinal disorders
Upper Gastrointestinal HaemorrhageGastrointestinal disorders
PneumoniaInfections and infestations
Pneumonia PneumococcalInfections and infestations
Urinary Tract InfectionInfections and infestations
Spinal Cord CompressionNervous system disorders
General Physical Health DeteriorationGeneral disorders
Pleural EffusionRespiratory, thoracic and mediastinal disorders
Hip FractureInjury, poisoning and procedural complications
Blood Bilirubin IncreasedInvestigations
DiarrhoeaGastrointestinal disorders
Hepatic Function AbnormalHepatobiliary disorders
Immune-Mediated HypothyroidismEndocrine disorders
Tumour Associated FeverNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Duodenal Ulcer HaemorrhageGastrointestinal disorders
Gastric PerforationGastrointestinal disorders
Intestinal PerforationGastrointestinal disorders
Intra-Abdominal HaemorrhageGastrointestinal disorders
Other adverse events (49 terms — click to expand)

ReactionSystemAtezolizumab + Bevacizumab:
AstheniaGeneral disorders
HypertensionVascular disorders
DiarrhoeaGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
Abdominal PainGastrointestinal disorders
Decreased AppetiteMetabolism and nutrition disorders
Covid-19Infections and infestations
ConstipationGastrointestinal disorders
ProteinuriaRenal and urinary disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back PainMusculoskeletal and connective tissue disorders
HypothyroidismEndocrine disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
HeadacheNervous system disorders
NasopharyngitisInfections and infestations
Abdominal Pain UpperGastrointestinal disorders
NauseaGastrointestinal disorders
Oedema PeripheralGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
HyperbilirubinaemiaHepatobiliary disorders
InsomniaPsychiatric disorders
AscitesGastrointestinal disorders
Mucosal InflammationGeneral disorders
Blood Bilirubin IncreasedInvestigations
Lipase IncreasedInvestigations
Platelet Count DecreasedInvestigations
DysphoniaRespiratory, thoracic and mediastinal disorders
HypertransaminasaemiaHepatobiliary disorders
PainGeneral disorders
Respiratory Tract InfectionInfections and infestations
MyalgiaMusculoskeletal and connective tissue disorders
Pain In ExtremityMusculoskeletal and connective tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Dry MouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Amylase IncreasedInvestigations
Weight DecreasedInvestigations
AnaemiaBlood and lymphatic system disorders

Most-reported serious reactions: Hepatic Encephalopathy, Oesophageal Varices Haemorrhage, Ascites, Back Pain, Hepatitis, Pyrexia, Abdominal Pain, Gastrointestinal Haemorrhage.

Data from ClinicalTrials.gov NCT04732286 adverse events section.

Sponsor's own description

This is a Phase IIIb, one arm, multicenter, open-label study primarily designed to evaluate the safety of atezolizumab + bevacizumab in participants with unresectable or unsuitable for locoregional treatments for metastatic HCC not previously treated with systemic therapy. As part of its secondary objectives, this study is also designed to evaluate the efficacy of atezolizumab and bevacizumab in these participants.

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. Overcoming physical stromal barriers to cancer immunotherapy.
    Chung SW, Xie Y, Suk JS. · · 2021 · cited 20× · PMID 34351575 · DOI 10.1007/s13346-021-01036-y
  5. 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
  6. Immunotherapy for advanced or recurrent hepatocellular carcinoma.
    Luo YZ, Zhu H. · · 2023 · cited 7× · PMID 37009314 · DOI 10.4251/wjgo.v15.i3.405
  7. Combination of immune checkpoint blockade and targeted gene regulation of angiogenesis for facilitating antitumor immunotherapy.
    Zhan J, Zhang M, Zhou L, He C. · · 2023 · cited 3× · PMID 36994358 · DOI 10.3389/fbioe.2023.1065773
  8. Systemic Therapy for Unresectable Hepatocellular Carcinoma: Current Landscape and Future Directions.
    Philippi Z, Reddy KD, Malik S, Al-Khalil Z, et al · · 2025 · cited 1× · PMID 40649773 · DOI 10.3390/ijms26135994

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