A Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab (IMbrave251)

• ClinicalTrials.gov Identifier: NCT04770896
• Recruitment Status: Recruiting
• First Posted: February 25, 2021
• Last Update Posted: March 21, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: February 23, 2021
• First Posted Date: February 25, 2021
• Last Update Posted Date: March 21, 2024
• Actual Study Start Date: April 26, 2021
• Estimated Primary Completion Date: September 23, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 23, 2021)

Overall Survival (OS) [ Time Frame: Randomization until death from any cause (approximately 42 months) ]

Overall survival (OS) is defined as the time from randomization into the study to death from any cause.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 20, 2024)

• Progression Free Survival (PFS) [ Time Frame: Randomization until the first occurrence of disease progression or death from any cause whichever occurs first (approximately 42 months) ]
  Progression free survival (PFS) is defined as the time from randomization into the study to the first occurrence of disease progression or death from any cause (whichever occurs first).
• Confirmed Objective Response Rate (ORR) [ Time Frame: Approximately 42 months ]
  Confirmed Objective Response Rate (ORR) is defined as the proportion of patients with a best response of either complete or partial response.
• Time to Progression (TTP) [ Time Frame: Randomization until the first occurrence of disease progression (approximately 42 months) ]
  Time to Progression (TTP) is defined as the time from randomization to the first occurrence of disease progression.
• Duration of Response (DOR) [ Time Frame: Time from the first occurrence of a confirmed documented objective response to disease progression or death from any cause whichever occurs first (approximately 42 months) ]
  Duration of Response (DOR) is defined as the time from the first occurrence of a documented confirmed objective response to disease progression or death from any cause (whichever occurs first).
• Time to confirmed deterioration (TTCD) [ Time Frame: Randomization to first deterioration maintained for two consecutive assessments, or one assessment followed by death from any cause wthin 3 weeks or 6 weeks (approximately 42 months) ]
  Time to confirmed deterioration (TTCD), of health-related quality of life (HRQoL), is defined as the time from randomization to first confirmed deterioration (decrease from baseline of ≥ 10 points) maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks (if Cycle 1-6) or 6 weeks (if after Cycle 6) in the following European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQC30) scales (separately): physical function, role function, and GHS/QoL.
• Percentage of Participants With Adverse Events [ Time Frame: Throughout study duration (approximately 42 months) ]
• Percentage of Participants With Adverse Events for Combination Treatment, Adverse Events Related to Atezolizumab, and TKI-Related Adverse Events [ Time Frame: Throughtout study (approximately 42 months) ]
• Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Throughout study (approximately 42 months) ]
• Serum Concentration of Atezolizumab [ Time Frame: At pre-defined intervals from first administration of study drug to approximately 42 months ]

Original Secondary Outcome Measures (submitted: February 23, 2021)

• Progression Free Survival (PFS) [ Time Frame: Randomization until the first occurrence of disease progression or death from any cause whichever occurs first (approximately 42 months) ]
  Progression free survival (PFS) is defined as the time from randomization into the study to the first occurrence of disease progression or death from any cause (whichever occurs first).
• Confirmed Objective Response Rate (ORR) [ Time Frame: Approximately 42 months ]
  Confirmed Objective Response Rate (ORR) is defined as the proportion of patients with a best response of either complete or partial response.
• Time to Progression (TTP) [ Time Frame: Randomization until the first occurrence of disease progression (approximately 42 months) ]
  Time to Progression (TTP) is defined as the time from randomization to the first occurrence of disease progression.
• Duration of Response (DOR) [ Time Frame: Time from the first occurrence of a confirmed documented objective response to disease progression or death from any cause whichever occurs first (approximately 42 months) ]
  Duration of Response (DOR) is defined as the time from the first occurrence of a confirmed documented objective response to disease progression or death from any cause (whichever occurs first).
• Time to deterioration (TTD) [ Time Frame: Randomization to first deterioration maintained for two consecutive assessments, or one assessment followed by death from any cause wthin 3 weeks or 6 weeks (approximately 42 months) ]
  Time to deterioration (TTD) is defined as the time from randomization to first deterioration (decrease from baseline of ≥ 10 points) maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks (if Cycle 1-6) or 6 weeks (if after Cycle 6) in the following European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30(EORTC QLQC30) scales (separately): physical function, role function, and GHS/QoL.
• Percentage of Participants With Adverse Events [ Time Frame: Throughout study duration (approximately 42 months) ]
• Percentage of Participants With Adverse Events for Combination Treatment, Adverse Events Related to Atezolizumab, and TKI-Related Adverse Events [ Time Frame: Throughtout study (approximately 42 months) ]
• Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Throughout study (approximately 42 months) ]
• Serum Concentration of Atezolizumab [ Time Frame: At pre-defined intervals from first administration of study drug to approximately 42 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab
• Official Title: A Phase III, Open-Label, Randomized Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab
• Brief Summary: This is a Phase III, open-label, multicenter, randomized, two-arm study designed to evaluate the efficacy and safety of atezolizumab plus either lenvatinib or sorafenib versus lenvatinib or sorafenib alone in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have progressed on prior systemic treatment with atezolizumab plus bevacizumab combination.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Unresectable Hepatocellular Carcinoma

Intervention

• Drug: Atezolizumab
  Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
  Other Name: Tecentriq
• Drug: Lenvatinib
  Lenvatinib will be administered once daily by mouth each day of every 21-day study treatment cycle. Participants with a baseline body weight of < 60 kg will receive a daily dose of 8 mg. Participants with a baseline body weight of ≥ 60 kg will receive a daily dose of 12 mg.
• Drug: Sorafenib
  Sorafenib will be administered at a dose of 800 mg per day, i.e. two tablets of 200 mg swallowed by mouth twice daily (equivalent to a total daily dose of 800 mg) each day of every 21-day study treatment cycle.

Study Arms

• Experimental: Atezolizumab + Lenvatinib or Sorafenib
  Participants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Lenvatinib
  • Drug: Sorafenib
• Active Comparator: Lenvatinib or Sorafenib
  Participants will receive lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
  Interventions:

  • Drug: Lenvatinib
  • Drug: Sorafenib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 23, 2021): 554
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2025
• Estimated Primary Completion Date: September 23, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/ cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients.
• Disease progression following prior atezolizumab plus bevacizumab combination treatment for HCC, for at least 4 consecutive treatment cycles, and 2 subsequent tumor assessments. It is required that at least 1 tumor assessment shows either stable disease (SD), partial response (PR), or complete response (CR).
• At least one measurable (per RECIST v1.1) target lesion that has not been previously treated with local therapy or, if the target lesion is within the field of previous local therapy, has subsequently progressed in accordance with RECIST v1.1.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 7 days prior to randomization
• Child-Pugh class A within 7 days prior to randomization
• Adequate hematologic and end-organ function

Exclusion Criteria:

• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
• History of leptomeningeal disease
• History of hepatic encephalopathy, preceding 6 months, unresponsive to therapy within 3 days
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: MO42541 https://forpatients.roche.com/; 888-662-6728 (U.S. and Canada); global.rochegenentechtrials@roche.com

• Listed Location Countries: Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Costa Rica, Croatia, Egypt, Estonia, Finland, France, Germany, Greece, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, Philippines, Russian Federation, Slovenia, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom

Administrative Information

• NCT Number: NCT04770896
• Other Study ID Numbers: MO42541
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical 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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: March 2024