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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Atezo + Bev 		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.
  • Drug: Atezolizumab
    Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.
    Other names:
    • Tecentriq
  • Drug: Bevacizumab
    Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
    Other names:
    • Avastin
  • Drug: Tiragolumab
    Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.
Experimental
Atezo + Bev +Tira 		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.
  • Drug: Atezolizumab
    Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.
    Other names:
    • Tecentriq
  • Drug: Bevacizumab
    Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
    Other names:
    • Avastin
  • Drug: Tiragolumab
    Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.
Experimental
Tobe + Bev 		Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.
  • Drug: Bevacizumab
    Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
    Other names:
    • Avastin
  • Drug: Tobemstomig
    Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1
    Other names:
    • RO7247669

Recruiting Locations

Georgetown University Medical Center
Washington, District of Columbia 20007

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: GO44457 https://forpatients.roche.com/
888-662-6728 (U.S. and Canada)
global.rochegenentechtrials@roche.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.