A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave150)

• ClinicalTrials.gov Identifier: NCT03434379
• Recruitment Status: Completed
• First Posted: February 15, 2018
• Results First Posted: November 5, 2021
• Last Update Posted: October 23, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Hepatocellular	Drug: Atezolizumab; Drug: Bevacizumab; Drug: Sorafenib	Phase 3

Detailed Description:

The participants will be randomized in a 2:1 ratio to one of the two treatment arms: Arm A (experimental arm): Atezolizumab +bevacizumab; Arm B (control arm): Sorafenib

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 558 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Open-Label, Randomized Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
• Actual Study Start Date: March 15, 2018
• Actual Primary Completion Date: August 31, 2020
• Actual Study Completion Date: November 17, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Atezolizumab + Bevacizumab; Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator	Drug: Atezolizumab; Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21 day cycle; Drug: Bevacizumab; Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21 day cycle
Active Comparator: Sorafenib; Participants will receive Sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator	Drug: Sorafenib; Sorafenib will be administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle

Outcome Measures

Primary Outcome Measures :

1. Overall Survival (OS) in the Global Population [ Time Frame: 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) ]
   OS was defined as the time from randomization to death from any cause.
2. Progression Free Survival by Independent Review Facility-Assessment (PFS-IRF) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the Global Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
   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).
3. Overall Survival (OS) in the China Population [ Time Frame: 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) ]
   OS was defined as the time from randomization to death from any cause.
4. PFS-IRF Per RECIST v1.1 in the China Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
   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).

Secondary Outcome Measures :

1. Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the Global Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
   ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
2. Objective Response Rate by IRF-Assessment (ORR-IRF) Per Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) in the Global Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
   ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
3. ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the Global Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
   ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
4. Duration of Response by IRF-Assessment (DOR-IRF) Per RECIST v1.1 in the Global Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
   DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.
5. Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the Global Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
   DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.
6. Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the Global Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
   DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.
7. PFS-IRF Per HCC mRECIST in the Global Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
   PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. 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).
8. PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the Global Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
   PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator 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).
9. Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the Global Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
   Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the 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).
10. TTP-IRF Per HCC mRECIST in the Global Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. 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).
11. TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the Global Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator 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).
12. Overall Survival by Baseline AFP in the Global Population [ Time Frame: From randomization to death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    OS was defined as the time from randomization to death from any cause. Subpopulations with baseline AFP <400 ng/mL and AFP>/= 400 ng/mL were analyzed.
13. PFS-IRF Per RECIST v1.1 by Baseline AFP in the Global Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the 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). Subpopulations with baseline AFP <400 ng/mL and AFP>/= 400 ng/mL were analyzed.
14. PFS-INV Per RECIST v1.1 by Baseline AFP in the Global Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator 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). Subpopulations with baseline AFP <400 ng/mL and AFP>/= 400 ng/mL were analyzed.
15. Time to Deterioration (TTD) in the Global Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    TTD was defined as the time from randomization to the first deterioration (decrease from baseline of >/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks.
16. Number of Participants With Adverse Events (AEs) in the Global Population [ Time Frame: Up to end of study (up to approximately 56 months) ]
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
17. Maximum Serum Concentration (Cmax) of Atezolizumab at Cycle 1 in the Global Population [ Time Frame: Post-dose on Day 1 of Cycle 1 (cycle length = 21 days) ]
18. Trough Serum Concentration (Cmin) of Atezolizumab in the Global Population [ Time Frame: Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days) ]
19. Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the Global Population [ Time Frame: Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 30 months) ]
20. Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the China Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
21. Objective Response Rate by IRF-Assessment (ORR-IRF) Per Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) in the China Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
22. ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the China Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
23. Duration of Response by IRF-Assessment (DOR-IRF) Per RECIST v1.1 in the China Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.
24. Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the China Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.
25. Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the China Population [ Time Frame: Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.
26. PFS-IRF Per HCC mRECIST in the China Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. 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).
27. PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the China Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator 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).
28. Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the China Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the 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).
29. TTP-IRF Per HCC mRECIST in the China Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. 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).
30. TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the China Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator 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).
31. Time to Deterioration (TTD) in the China Population [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) ]
    TTD was defined as the time from randomization to the first deterioration (decrease from baseline of >/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks.
32. Number of Participants With Adverse Events (AEs) in the China Population [ Time Frame: Up to end of study (up to approximately 56 months) ]
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
33. Maximum Serum Concentration (Cmax) of Atezolizumab in the China Population [ Time Frame: Post-dose on Day 1 of Cycle 1 (cycle length = 21 days) ]
34. Trough Serum Concentration (Cmin) of Atezolizumab in the China Population [ Time Frame: Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days) ]
35. Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the China Population [ Time Frame: Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 18 months) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC)
• No prior systemic therapy for HCC. Previous use of herbal therapies/traditional Chinese medicines with anti-cancer activity included in the label is allowed, provided that these medications are discontinued prior to randomization.
• At least one measurable untreated lesion
• ECOG Performance Status of 0 or 1
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent
• For men: agreement to remain abstinent
• Child-Pugh class A

Exclusion Criteria:

• History of leptomeningeal disease
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
• Known active tuberculosis
• History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 1 month after the last dose of sorafenib
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
• Moderate or severe ascites
• History of hepatic encephalopathy
• Co-infection of HBV and HCV
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled or symptomatic hypercalcemia
• Treatment with systemic immunostimulatory agents
• Inadequately controlled arterial hypertension
• Prior history of hypertensive crisis or hypertensive encephalopathy
• Evidence of bleeding diathesis or significant coagulopathy
• History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration
• Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
• Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses
• Local therapy to liver within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure
• Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)

Contacts and Locations

Locations

United States, Arizona

St. Josephs Hospital and Medical Center

Phoenix, Arizona, United States, 85260

United States, California

City of Hope

Duarte, California, United States, 91010

Uni of California - San Diego; Cancer Center & Dept of Medicine

La Jolla, California, United States, 92093

Kaiser Permanente Northern California

Novato, California, United States, 94589

University of California Irvine Medical Center

Orange, California, United States, 92868

Kaiser Permanente Sacramento Medical Center

Sacramento, California, United States, 95825

California Pacific Medical Center

San Francisco, California, United States, 94115

Kaiser Permanente - San Francisco Medical Center

San Francisco, California, United States, 94118

University of California Los Angeles

Santa Monica, California, United States, 90404

Kaiser Permanente - Walnut Creek

Walnut Creek, California, United States, 94596

United States, Colorado

Banner MD Anderson Cancer Center

Greeley, Colorado, United States, 85234

United States, District of Columbia

Georgetown University

Washington, District of Columbia, United States, 20007

United States, Florida

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Michigan

Henry Ford Health System

Detroit, Michigan, United States, 48202

United States, Missouri

Washington University; Wash Uni. Sch. Of Med

Saint Louis, Missouri, United States, 63110

United States, New Mexico

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, United States, 87102

United States, New York

Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

New York, New York, United States, 10016

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

United States, Texas

M.D Anderson Cancer Center; Uni of Texas At Houston

Houston, Texas, United States, 77030

United States, Washington

Swedish Cancer Inst.

Seattle, Washington, United States, 98104

Australia, New South Wales

Bankstown-Lidcombe Hospital

Bankstown, New South Wales, Australia, 2200

St George Hospital

Kogarah, New South Wales, Australia, 2217

Australia, South Australia

The Queen Elizabeth Hospital

Woodville, South Australia, Australia, 5011

Australia, Victoria

Sunshine Hospital

St Albans, Victoria, Australia, 3021

Canada, Ontario

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada, K1Y 4E9

Canada, Quebec

Centre hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, Canada, H2X 0A9

Jewish General Hospital

Montreal, Quebec, Canada, H3T 1E2

McGill University Health Centre - Glen Site

Montreal, Quebec, Canada, H4A 3J1

China

Peking Union Medical College Hospital

Beijing City, China, 100032

Beijing Friendship Hospital

Beijing, China, 100050

Beijing Cancer Hospital

Beijing, China, 100142

the First Hospital of Jilin University

Changchun, China, 130021

Jilin Cancer Hospital

Changchun, China, 132013

Hunan Cancer Hospital

Changsha CITY, China, 410013

The First People's Hospital of Foshan; Local Ethic Committee

Foshan, China, 510000

The 900th Hospital of PLA joint service support force

Fuzhou, China, 110016

Sun Yet-sen University Cancer Center

Guangzhou City, China, 510663

Nanfang Hospital, Southern Medical University

Guangzhou, China, 510515

Sir Run Run Shaw Hospital

Hangzhou City, China, 310018

Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department

Hangzhou City, China, 310022

The First Affiliated Hospital of College of Medicine, Zhejiang University

Hangzhou, China, 310003

Harbin Medical University Cancer Hospital

Harbin, China, 150081

Anhui Province Cancer Hospital

Hefei City, China, 230031

The First Affiliated Hospital of Anhui Medical University

Hefei, China, 230022

General Hospital of Jinan Military Command of PLA

Jinan, China, 250031

The 81st Hospital of P.L.A.

Nanjing City, China, 210002

Fudan University Shanghai Cancer Center

Shanghai City, China, 200120

Zhongshan Hospital Fudan University

Shanghai, China, 200032

Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech

Wuhan, China, 430030

Czechia

Masarykuv onkologicky ustav

Brno, Czechia, 656 53

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, Czechia, 779 00

France

Hopital Claude Huriez;Gastro Enterologie

Lille, France, 59037

Hopital De La Croix Rousse; Hepatologie Gastro Enterologie

Lyon, France, 69317

Hopital Timone Adultes; Gastro Enterologie

Marseille, France, 13385

Hopital Saint-Eloi; Hepatologie-Gastro-Enterologie

Montpellier, France, 34295

Hopital Hotel Dieu Et Hme; Hepatologie Gastro Enterologie

Nantes, France, 44093

CHU Nice - Hôpital de l'Archet 2; service Hepato gastro enterologie

Nice Cedex, France, 06202

Hopital Charles Nicolle; Gastroenterologie

Rouen, France, 76031

Hopital Hautepierre; Gastro Enterologie

Strasbourg, France, 67098

Hôpital d'Adultes; Service hépato-gastro-entérologie

Vandoeuvre-les-nancy, France, 54511

Institut Gustave Roussy; Gastro-Enterologie

Villejuif, France, 94805

Germany

Campus Virchow-Klinikum Charité Centrum 13; Medizinische Klinik; Abt.Hepatologie u.Gastroenterologie

Berlin, Germany, 13353

Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I

Frankfurt, Germany, 60590

Universitaetsklinikum Hamburg-Eppendorf; I. Medizinische Klinik - Gastroenterologie

Hamburg, Germany, 20246

Med. Hochschule Hannover; Gastroenterologie

Hannover, Germany, 30625

Universitätsklinikum Leipzig Medizinische Klinik II Gastroenterolog. u. Hepatolog.

Leipzig, Germany, 04103

Uniklinik Mainz; I. Medizinische Klinik

Mainz, Germany, 55131

Klinikum der Uni Regensburg; Klinik f.Innere Medizin I Abt. Hämatologie und Internistische Onkologie

Regensburg, Germany, 93053

Hong Kong

Queen Mary Hospital; Dept. Of Haematology & Oncology

Hong Kong, Hong Kong

Prince of Wales Hosp; Dept. Of Clinical Onc

Shatin, Hong Kong

Italy

Az. Osp. Rummo; Oncologia Medica

Benevento, Campania, Italy, 82100

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

Meldola, Emilia-Romagna, Italy, 47014

Az. Osp. S. Luigi Gonzaga; Divisione Di Oncologia Medica

Orbassano, Piemonte, Italy, 10043

A.O.U. Cagliari-P.O. Monserrato;U.O. Oncologia

Cagliari, Sardegna, Italy, 09100

Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico

Pisa, Toscana, Italy, 56126

IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima

Padova, Veneto, Italy, 35128

Japan

Chiba University Hospital

Chiba, Japan, 260-8677

National Cancer Center Hospital East

Chiba, Japan, 277-8577

Kurume University Hospital

Fukuoka, Japan, 830-0011

Sapporo Kosei Genaral Hospital

Hokkaido, Japan, 060-0033

Hokkaido University Hospital

Hokkaido, Japan, 060-8648

Kanazawa University Hospital

Ishikawa, Japan, 920-8641

Kitasato University Hospital

Kanagawa, Japan, 252-0375

Kumamoto University Hospital

Kumamoto, Japan, 860-8556

Osaka Metropolitan University Hospital

Osaka, Japan, 545-8586

Kindai University Hospital

Osaka, Japan, 589-8511

Saga-ken Medical Centre Koseikan

Saga, Japan, 840-8571

Shizuoka Cancer Center

Shizuoka, Japan, 411-8777

Japanese Red Cross Musashino Hospital

Tokyo, Japan, 180-8610

Korea, Republic of

Chonnam National University Hwasun Hospital

Jeollanam-do, Korea, Republic of, 58128

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 03722

Asan Medical Center

Seoul, Korea, Republic of, 05505

Samsung Medical Center

Seoul, Korea, Republic of, 06351

Ulsan University Hosiptal

Ulsan, Korea, Republic of, 44033

Poland

Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii

Gdansk, Poland, 80-219

ID Clinic

Myslowice, Poland, 41-400

SP ZOZ MSWiA z WARMINSKO-MAZURSKIM CENTRUM ONKOLOGII; CLINICAL ONCOLOGY, CLINICAL IMMUNOLOGY

Olsztyn, Poland, 10-228

Narodowy Instytut Onkologii im. Marii Sk?odowskiej-Curie - Pa?stwowy Instytut Badawczy

Warszawa, Poland, 02-781

Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii

Wroc?aw, Poland, 53-413

Russian Federation

FSBI "National Medical Research Center of Oncology N.N. Blokhin?; Clinical Biotechnologies

Moscow, Moskovskaja Oblast, Russian Federation, 115478

GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)

Saint Petersburg, Sankt Petersburg, Russian Federation, 197758

Singapore

National Cancer Centre

Singapore, Singapore, 169610

Tan Tock Seng Hospital; Oncology

Singapore, Singapore, 308433

Spain

Hospital Universitari Vall d'Hebron; Oncology

Barcelona, Spain, 08035

Hospital Clinico San Carlos; Servicio de Oncologia

Madrid, Spain, 28040

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, Spain, 28046

Centro Integral Oncologico Clara Campal; Servicio de Oncología

Madrid, Spain, 28050

Hospital Universitario Miguel Servet; Servicio de Oncologia Medica

Zaragoza, Spain, 50009

Taiwan

National Cheng Kung University Hospital; Oncology

Tainan, Taiwan, 00704

Chi-Mei Medical Centre; Hematology & Oncology

Tainan, Taiwan, 710

Veterans General Hospital; Cancer Center

Taipei, Taiwan, 00112

National Taiwan Uni Hospital; Dept of Oncology

Taipei, Taiwan, 100

Chang Gung Memorial Hospital-Linkou; Dept of Oncology

Taoyuan County, Taiwan, 333

United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 0YN

Royal Free Hospital; Dept of Oncology

London, United Kingdom, NW3 2QG

King'S College Hospital

London, United Kingdom, SE5 9RS

Christie Hospital Nhs Trust; Medical Oncology

Manchester, United Kingdom, M2O 4BX

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:

Study Protocol  [PDF] February 1, 2021

Statistical Analysis Plan  [PDF] February 22, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kaseb AO, Guan Y, Gok Yavuz B, Abbas AR, Lu S, Hasanov E, Toh HC, Verret W, Wang Y. Serum IGF-1 Scores and Clinical Outcomes in the Phase III IMbrave150 Study of Atezolizumab Plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2022 Oct 11;9:1065-1079. doi: 10.2147/JHC.S369951. eCollection 2022.

Li Y, Liang X, Li H, Chen X. Atezolizumab plus bevacizumab versus nivolumab as first-line treatment for advanced or unresectable hepatocellular carcinoma: A cost-effectiveness analysis. Cancer. 2022 Nov 15;128(22):3995-4003. doi: 10.1002/cncr.34457. Epub 2022 Sep 16.

Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Lim HY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Ma N, Nicholas A, Wang Y, Li L, Zhu AX, Finn RS. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022 Apr;76(4):862-873. doi: 10.1016/j.jhep.2021.11.030. Epub 2021 Dec 11.

Salem R, Li D, Sommer N, Hernandez S, Verret W, Ding B, Lencioni R. Characterization of response to atezolizumab + bevacizumab versus sorafenib for hepatocellular carcinoma: Results from the IMbrave150 trial. Cancer Med. 2021 Aug;10(16):5437-5447. doi: 10.1002/cam4.4090. Epub 2021 Jun 29.

Galle PR, Finn RS, Qin S, Ikeda M, Zhu AX, Kim TY, Kudo M, Breder V, Merle P, Kaseb A, Li D, Mulla S, Verret W, Xu DZ, Hernandez S, Ding B, Liu J, Huang C, Lim HY, Cheng AL, Ducreux M. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Jul;22(7):991-1001. doi: 10.1016/S1470-2045(21)00151-0. Epub 2021 May 27.

Wen F, Zheng H, Zhang P, Liao W, Zhou K, Li Q. Atezolizumab and bevacizumab combination compared with sorafenib as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma: A cost-effectiveness analysis in China and the United states. Liver Int. 2021 May;41(5):1097-1104. doi: 10.1111/liv.14795. Epub 2021 Feb 8.

Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03434379
• Other Study ID Numbers: YO40245; 2017-003691-31 ( EudraCT Number )
• First Posted: February 15, 2018
• Results First Posted: November 5, 2021
• Last Update Posted: October 23, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Bevacizumab; Atezolizumab; Sorafenib; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immune Checkpoint Inhibitors