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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
62
Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.
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.
Time frame: At the time of surgery
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.
Time frame: At the time of surgery
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.
Time frame: 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.
Time frame: Randomization up to approximately 3 years
Overall Survival (OS)
OS is defined as the time from randomization to death from any cause.
Time frame: 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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1
University of Southern California (USC)
Los Angeles, California, United States
University of California Los Angeles (UCLA) - Cancer Care - Santa Monica
Santa Monica, California, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus
Detroit, Michigan, United States
Columbia University Medical Center
New York, New York, United States
UT Southwestern Medical Center
Dallas, Texas, United States
Klinikum Klagenfurt am Wörthersee
Klagenfurt, Austria
Wiener Gesundheitsverbund, Klinik Favoriten
Vienna, Austria
Department of Internal Medicine III AKH and Medical University of Vienna
Vienna, Austria
Centre Georges Francois Leclerc (CGFL)
Dijon, France
...and 20 more locations
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At the time of surgery
Percentage of Participants With Adverse Events
Time frame: 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).
Time frame: >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.
Time frame: 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
Time frame: Within 90 days after surgery