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

• Register: ClinicalTrials.gov
• Last refreshed on: 5 December 2022
• Main ID: NCT03434379
• Date of registration: 31/01/2018
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma IMbrave150
• Scientific 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
• Date of first enrolment: March 15, 2018
• Target sample size: 558
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03434379
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Canada, China, Czechia, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Singapore, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Carcinoma, Hepatocellular

Intervention(s)

Drug: Atezolizumab

Drug: Bevacizumab

Drug: Sorafenib

Primary Outcome(s)

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)]

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)]

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)]

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)]

Secondary Outcome(s)

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

Percentage of Participants With Adverse Events (AEs) in the China Population [Time Frame: Up to end of study (up to approximately 40 months)]

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)]

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)]

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)]

Maximum Serum Concentration (Cmax) of Atezolizumab in the China Population [Time Frame: Post-dose on Day 1 of Cycle 1 (cycle length = 21 days)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

Percentage of Participants With Adverse Events (AEs) in the Global Population [Time Frame: Up to end of study (up to approximately 40 months)]

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-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)]

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)]

Secondary ID(s)

YO40245

2017-003691-31

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/11/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03434379