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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05908786
Other study ID # GO44457
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date December 5, 2023
Est. completion date September 30, 2028

Study information

Verified date June 2024
Source Hoffmann-La Roche
Contact Reference Study ID Number: GO44457 https://forpatients.roche.com
Phone 888-662-6728 (U.S. and Canada)
Email global.rochegenentechtrials@roche.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 150
Est. completion date September 30, 2028
Est. primary completion date September 30, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Diagnosis of HCC confirmed either histologically or clinically according to AASLD criteria for patients with cirrhosis. For participants without cirrhosis, histological confirmation is mandatory. - HCC that is amenable to R0 surgical resection with curative intent in the opinion of the surgeons and oncologists or hepatologists involved in the care of the participant. Patients presenting with resectable HCC within or beyond Milan criteria (without extrahepatic spread or macrovascular invasion) are eligible. - Measurable disease (at least one target lesion) according to RECIST v1.1 as determined by the investigator - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization - Child-Pugh Class A within 7 days prior to randomization - Negative HIV test at screening - No prior locoregional or systemic treatment for HCC - Adequate hematologic and end-organ function - Documented virology status of hepatitis - For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception - For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm General Exclusion Criteria: - Presence of extrahepatic disease or macrovascular invasion - Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC, or other rare variants of HCC - History of hepatic encephalopathy if clinically significant within one year prior to initiation of study treatment - Moderate or severe ascites - Active co-infection with HBV and HCV - Known active co-infection with HBV and hepatitis D viral infection - Prior treatment with CD137 agonists or immune checkpoint inhibitors, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies - Treatment with investigational therapy within 28 days prior to initiation of study treatment - Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding - A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment - Inadequately controlled hypertension - History of hypertensive crisis or hypertensive encephalopathy - Significant vascular disease within 6 months prior to initiation of study treatment - History of hemoptysis within 1 month prior to initiation of study treatment - Evidence of bleeding diathesis or significant coagulopathy - Current or recent (<= 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes - History of abdominal or tracheoesophageal fistula, GI perforation or intra-abdominal abscesses within 6 months prior to initiation of study treatment - History of intestinal obstruction and/or clinical sign or symptoms of GI obstruction - Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture - Grade >= proteinuria - Major surgical procedure, open biopsy, or significant traumatic injury, or abdominal surgery, interventions or traumatic injuries, or anticipation of need of major surgical procedure other than potentially curative liver resection - Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID) - Serious infection requiring oral or IV antibiotics and/or hospitalization - Active tuberculosis

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.
Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
Tiragolumab
Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.
Tobemstomig
Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1

Locations

Country Name City State
France Centre Georges Francois Leclerc (CGFL) Dijon
France Centre Eugene Marquis (CEM) Rennes
France Assistance Publique-Hopitaux de Paris Villejuif
France Gustave Roussy Villejuif
Germany Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz; Medizinische Klinik und Poliklinik Mainz
Korea, Republic of CHA Bundang Medical Center Gyeonggi-do
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Severance Hospital, Yonsei University Health System Seoul
New Zealand Auckland District Health Board (ADHB); Auckland City Hospital (ACH) Auckland
Spain Hospital Clinic de Barcelona (Hospital Clinic i Provincial); Barcelona Clinic Liver Cancer (BCLC) Barcelona
Spain Hospital Universitario Fundacion Jimenez Diaz. Madrid
Spain Clínica Universidad de Navarra Pamplona Navarra
Spain Hospital Universitario Marques de Valdecilla Santander Cantabria
Taiwan Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital Tainan
Taiwan National Cheng Kung University Hospital Tainan
Taiwan Taipei Veterans General Hospital Taipei City
Taiwan National Taiwan University Hospital (NTUH) - Cancer Research Center Zhongzheng Dist.
United Kingdom Belfast Health and Social Care Trust - Belfast City Hospital Belfast
United Kingdom Imperial College London - Imperial Centre for Translational and Experimental Medicine (ICTEM) London
United States Montefiore Einstein Cancer Center Bronx New York
United States UT Southwestern Medical Center Dallas Texas
United States Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus Detroit Michigan
United States University of Southern California (USC); Norris Comprehensive Cancer Center Los Angeles California
United States Yale School of Medicine - Smilow Cancer Hospital - Yale-New Haven Hospital Location New Haven Colorado
United States Columbia University Medical Center; Herbert Irving Pavilion Location New York New York
United States University of Pennsylvania - Abramson Cancer Center Philadelphia Pennsylvania
United States University of California Los Angeles (UCLA) - Cancer Care - Santa Monica Santa Monica California
United States Fred Hutchinson/University of Washington Cancer Consortium Seattle Washington
United States Georgetown University Medical Center Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  France,  Germany,  Korea, Republic of,  New Zealand,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Secondary 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
Secondary Relapse-Free Survival (RFS) 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)
Secondary 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
Secondary 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)
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary Percentage of Participants With Adverse Events Up to approximately 3 years after first participant enrolled
Secondary 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
Secondary 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)
Secondary Post-Operative Mortality Post-operative mortality is defined as death within 90 days after surgery Within 90 days after surgery
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