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This is a Phase Ib/II, open-label, multicenter, randomized platform study to evaluate neoadjuvant immunotherapy combinations in participants with resectable HCC. The study is designed with the flexibility to open new treatment arms as new agents become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the participant population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atezo + Bev | Experimental | Participants in the atezolizumab plus bevacizumab (Atezo + Bev) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first. |
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| Atezo + Bev +Tira | Experimental | Participants in the atezolizumab plus bevacizumab plus tiragolumab (Atezo + Bev +Tira) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first. |
|
| Tobe + Bev | Experimental | Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first. Enrollment is closed. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Major Pathologic Response (MPR) Rate | MPR rate is defined as the proportion of participants with =<10% residual viable tumor in the tumor bed at the time of surgery, as assessed by central pathological review. | At the time of surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Pathologic Complete Response (pCR) Rate | pCR rate is defined as the proportion of participants with an absence of residual tumor at the time of surgery, as assessed by central pathological review. | At the time of surgery |
| Relapse-Free Survival (RFS) |
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Inclusion Criteria:
General Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Southern California (USC) | Los Angeles | California | 90033 | United States | ||
| University of California Los Angeles (UCLA) - Cancer Care - Santa Monica |
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
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| Bevacizumab | Drug | Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1. |
|
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| Tiragolumab | Drug | Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1. |
|
| Tobemstomig | Drug | Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1 |
|
|
RFS is defined as the time from surgery to the first documented recurrence of disease (intrahepatic or extrahepatic) according to EASL and/or RECIST v1.1, or death from any cause.
| Surgery to the first documented recurrence of disease (up to approximately 2 years) |
| Event-Free Survival (EFS) | EFS is defined as the time from randomization to any of the following events (whichever occurs first): disease progression that precludes surgery, as assessed by the investigator according RECIST v1.1; local regional, or distant disease recurrence as measured by EASL and/or RECIST v1.1; or death from any cause. | Randomization up to approximately 3 years |
| Overall Survival (OS) | OS is defined as the time from randomization to death from any cause. | Randomization to death from any cause (up to approximately 3 years) |
| OS Rate at 24 Months | OS rate at 24 months is defined as the proportion of participants who have not experience death from any cause at 24 months after randomization. | Randomization up to 24 months |
| OS Rate at 36 Months | OS rate at 36 months is defined as the proportion of participants who have not experience death from any cause at 36 months after randomization. | Randomization up to 36 months |
| Objective Response Rate (ORR) | ORR is defined as the proportion of participants with a radiographic Complete Response (CR) or Partial Response (PR) prior to surgery, as determined by the investigator according to RECIST v1.1 and HCC mRECIST. Responses will be assessed and determined according to RECIST v1.1 and HCC mRECIST but are not required to be confirmed by subsequent imaging assessments. | Prior to surgery |
| Proportion of Participants Downstaged to Within Milan Criteria | Proportion of participants downstaged to within Milan criteria (for participants beyond criteria at randomization). Within Milan criteria is defined as single tumor <= 5 cm or 2 - 3 nodules all <= 3 cm. | Prior to surgery |
| R0 Resection Rate | R0 resection rate (proportion of resected participants obtaining an R0 resection). R0 resection is defined as a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed. | At the time of surgery |
| Percentage of Participants With Adverse Events | Up to approximately 3 years after first participant enrolled |
| Proportion of Participants With Delayed or Canceled Surgery Due to Treatment-Related Adverse Events | Proportion of participants with delayed or canceled surgery due to treatment-related adverse events (defined as > 28 days from surgical restaging visit). | >28 days from surgical restaging visit, anticipated up to 56 days |
| Post-Operative Surgical Complication Rates According to The Clavien-Dindo Surgical Classification | Post-operative surgical complication rates according to the Clavien-Dindo surgical classification. Clinically relevant complications are defined as Clavien-Dindo Grade >= IIIa. | Surgery to treatment completion/discontinuation (up to approximately 2 years) |
| Post-Operative Mortality | Post-operative mortality is defined as death within 90 days after surgery | Within 90 days after surgery |
| Santa Monica |
| California |
| 90404-2023 |
| United States |
| Georgetown University Medical Center | Washington D.C. | District of Columbia | 20007 | United States |
| Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus | Detroit | Michigan | 48201-2013 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| UT Southwestern Medical Center | Dallas | Texas | 75390-8813 | United States |
| Klinikum Klagenfurt am Wörthersee | Klagenfurt | 9020 | Austria |
| Wiener Gesundheitsverbund, Klinik Favoriten | Vienna | 1100 | Austria |
| Department of Internal Medicine III AKH and Medical University of Vienna | Vienna | 1180 | Austria |
| Centre Georges Francois Leclerc (CGFL) | Dijon | 21079 | France |
| Centre Eugene Marquis (CEM) | Rennes | 35042 | France |
| Assistance Publique-Hopitaux de Paris | Villejuif | 94800 | France |
| Gustave Roussy | Villejuif | 94800 | France |
| University Essen | Essen | 45147 | Germany |
| Universitaets Klinikum Frankfurt - Zentrum der Inneren Medizin | Frankfurt | 60596 | Germany |
| Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz | Mainz | 55131 | Germany |
| Auckland District Health Board (ADHB) | Auckland | 1023 | New Zealand |
| CHA Bundang Medical Center | Seongnam-si | Gyeonggi-do | 463-712 | South Korea |
| Severance Hospital, Yonsei University Health System | Seoul | 003-722 | South Korea |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Hospital Universitario Marques de Valdecilla | Santander | Cantabria | 39008 | Spain |
| Clínica Universidad de Navarra | Pamplona | Navarre | 31620 | Spain |
| Hospital Clinic de Barcelona (Hospital Clinic i Provincial) | Barcelona | 8036 | Spain |
| Hospital Universitario Fundacion Jimenez Diaz. | Madrid | 28040 | Spain |
| Taichung Veterans General Hospital | Taichung | 40705 | Taiwan |
| National Cheng Kung University Hospital | Tainan | 70457 | Taiwan |
| Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital | Tainan | 83301 | Taiwan |
| Taipei Veterans General Hospital | Taipei | 112 | Taiwan |
| National Taiwan University Hospital (NTUH) - Cancer Research Center | Zhongzheng Dist. | 10051 | Taiwan |
| Imperial College London - Imperial Centre for Translational and Experimental Medicine (ICTEM) | London | United Kingdom |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jul 9, 2026 |
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
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| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| D000068258 | Bevacizumab |
| C000730814 | Tiragolumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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