A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma

NCT05908786 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: GO44457
• Study Type: interventional
• Target: 62
• Locations: 6 countries
• Sites: 14

Brief 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.

Conditions

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (1)

• Major Pathologic Response (MPR) Rate

  MPR rate was defined as the percentage of participants who had achieved MPR and was estimated for each treatment cohort in the efficacy-evaluable population. MPR was defined as ≤ 10% residual viable tumor in the tumor bed at the time of surgical resection in the primary tumor, as assessed by the central pathology laboratory. Participants who did not proceed to surgery were considered as non-responders for MPR. Percentages have been rounded off.

  At the time of surgery (up to 15 weeks)

Secondary Outcomes (19)

• Pathologic Complete Response (pCR) Rate

  At the time of surgery (up to 15 weeks)

• Relapse-free Survival (RFS), as Assessed by the Investigator According to European Association for the Study of the Liver (EASL) and/or Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

  From surgery to the first documented recurrence of disease (up to 20.5 months)

• Event-free Survival (EFS), as Assessed by the Investigator According to EASL and RECIST v1.1

  From randomization to PD that precluded surgery or disease recurrence or death from any cause, whichever occurred first (up to 20.5 months)

• Overall Survival (OS)

  From randomization to death from any cause (up to 20.5 months)

• OS Rate at 6 Months, 12 Months, and 18 Months

  At Months 6, 12, and 18

Study Arms (3)

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.

Drug: Atezolizumab; Drug: Bevacizumab

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.

Drug: Atezolizumab; Drug: Bevacizumab; Drug: Tiragolumab

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.

Drug: Bevacizumab; Drug: Tobemstomig

Interventions

Atezolizumab DRUG

Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.

Also known as: Tecentriq

Atezo + Bev; Atezo + Bev +Tira

Bevacizumab DRUG

Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.

Also known as: Avastin

Atezo + Bev; Atezo + Bev +Tira; Tobe + Bev

Tiragolumab DRUG

Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.

Atezo + Bev +Tira

Tobemstomig DRUG

Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1

Also known as: RO7247669

Tobe + Bev

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (14)

University of Southern California (USC)

Los Angeles, California, 90033, United States

Location

University of California Los Angeles (UCLA) - Cancer Care - Santa Monica

Santa Monica, California, 90404-2023, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390-8813, United States

Location

Klinikum Klagenfurt am Wörthersee

Klagenfurt, 9020, Austria

Location

Department of Internal Medicine III AKH and Medical University of Vienna

Vienna, 1090, Austria

Location

Centre Georges Francois Leclerc (CGFL)

Dijon, 21079, France

Location

Gustave Roussy

Villejuif, 94800, France

Location

University Essen

Essen, 45147, Germany

Location

Universitaets Klinikum Frankfurt - Zentrum der Inneren Medizin

Frankfurt, 60596, Germany

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz.

Madrid, 28040, Spain

Location

Imperial College London - Imperial Centre for Translational and Experimental Medicine (ICTEM)

London, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab; Tiragolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: June 18, 2023
• Study Start: December 5, 2023
• Primary Completion: August 27, 2025
• Study Completion: November 13, 2025
• Last Updated: September 15, 2026
• Results First Posted: September 15, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share

Locations

ES (2); US (5); DE (2); FR (2); GB (1); AU (2)