A Study of Atezolizumab (Tecentriq) in Combination With Bevacizumab to Investigate Safety and Efficacy in Patients With Unresectable Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy-Amethista

NCT04487067 | Completed Phase 3 Results

• 1 other identifier: ML42243
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 21

Brief Summary

This is a Phase IIIb, one arm, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab + bevacizumab in patients with unresectable HCC who have received no prior systemic treatment.

Conditions

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Grade 3-5 National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE V5) Bleeding/Haemorrhage

  An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Severity of AEs was graded using NCI CTCAE v5.0. Grade 3=Severe/medically significant but not immediately life-threatening, hospitalization/prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4=Life-threatening consequences, urgent intervention indicated; Grade 5=Death related to AE.

  Up to approximately 47.6 months

Secondary Outcomes (9)

• Overall Survival (OS)

  Up to approximately 47.6 months

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Up to approximately 47.6 months

• Progression-free Survival (PFS)

  Up to approximately 47.6 months

• Objective Response Rate (ORR)

  Up to approximately 47.6 months

• Time to Progression (TTP)

  Up to approximately 47.6 months

Other Outcomes (1)

• Number of Participants Starting Second or Further Lines of Treatment

  Up to approximately 47.6 months

Study Arms (1)

Atezolizumab + Bevacizumab

EXPERIMENTAL

Participants will receive atezolizumab 1200 mg intravenous (IV) infusions Q3W (dosed in 3-week cycles) + bevacizumab 15 mg/kg IV Q3W (dosed in 3-week cycles)

Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Atezolizumab DRUG

Atezolizumab 1200 mg IV infusion q3w

Also known as: Tecentriq

Atezolizumab + Bevacizumab

Bevacizumab DRUG

Bevacizumab 15 mg/kg IV Q3W

Also known as: Avastin

Atezolizumab + Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Unresectable HCC with diagnosis confirmed by histology, with a biopsy within 6 months from recruitment;
• Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies;
• No prior systemic therapy for HCC;
• At least one measurable untreated lesion;
• Patients who received prior local therapy are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST version 1.1;
• ECOG Performance Status of 0 or 1 within 7 days prior to recruitment;
• Child-Pugh class A within 7 days prior to recruitment;
• Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed. In case of varices at high risk of bleeding (corresponding to medium (F2) or large (F3) varices, or F1 varices with cherry red spots or red wale marking) prophylatic treatment per local standard of care must be adopted prior to enrollment. Patients who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure provided they had no varices at high risk of bleeding;
• Adequate hematologic and end-organ function
• Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade \<= 1 prior to study entry, with the exception of alopecia
• Negative HIV test at screening with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥200µL, and have an undetectable viral load;
• In patients with viral HCC, documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test;
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.

You may not qualify if:

• History of leptomeningeal disease or brain metastases;
• Active or history of autoimmune disease or immune deficiency;
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan;
• Known active tuberculosis;
• Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina;
• History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death;
• Prior allogeneic stem cell or solid organ transplantation;
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of atezolizumab and 6 months after the last dose of bevacizumab;
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC;
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding;
• A prior bleeding event due to oesophageal and/or gastric varices within 6 months prior to initiation of study treatment;
• Clinically evident ascites;
• Co-infection of HBV and HCV;
• Co-infection with HBV and hepatitis D viral infection;
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases;

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (21)

IRCCS Ospedale Casa Sollievo Della Sofferenza

San Giovanni Rotondo, Apulia, 71013, Italy

Location

Fondazione Pascale

Napoli, Campania, 80100, Italy

Location

Azienda Osp Uni Seconda Università Degli Studi Di Napoli

Napoli, Campania, 80131, Italy

Location

Ospedale del Mare

Napoli, Campania, 80147, Italy

Location

A.O. S. Orsola Malpighi

Bologna, Emilia-Romagna, 40138, Italy

Location

Arcispedale Santa Maria Nuova

Reggio Emilia, Emilia-Romagna, 42100, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Rome, Lazio, 00151, Italy

Location

Policlinico Universitario Agostino Gemelli

Rome, Lazio, 00168, Italy

Location

A.O. Universitaria S. Martino Di Genova

Genoa, Liguria, 16132, Italy

Location

Ospedali Riuniti - Bergamo

Bergamo, Lombardy, 24128, Italy

Location

Fondazione IRCCS Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

Istituto Nazionale Dei Tumori

Milan, Lombardy, 20133, Italy

Location

Istituto Clinico Humanitas

Rozzano, Lombardy, 20089, Italy

Location

Azienda Ospedaliera Ordine Mauriziano di Torino

Turin, Piedmont, 10128, Italy

Location

A.O.U. Cagliari-P.O. Monserrato

Cagliari, Sardinia, 09100, Italy

Location

A.O.U. Policlinico Paolo Giaccone

Palermo, Sicily, 90127, Italy

Location

Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi

Palermo, Sicily, 90127, Italy

Location

A.O.U Careggi

Florence, Tuscany, 50124, Italy

Location

Azlenda Ospendaliero-Universitaria Pisana

Pisa, Tuscany, 56100, Italy

Location

Clinica Oncologica-Ospedali Riuniti Ancona

Torrette, Tuscany, 60020, Italy

Location

IOV - Istituto Oncologico Veneto - IRCCS

Padua, Veneto, 35128, Italy

Location

Related Publications (1)

• Piscaglia F, Masi G, Martinelli E, Cabibbo G, Di Maio M, Gasbarrini A, Iavarone M, Antonuzzo L, Mazzaferro V, Ballestrero A, Garufi C, Bergamo F, Celsa C, Marino D, Tovoli F, Ponziani FR, Pressiani T, Astolfi C, Gazzoli GC, Ciardiello F, Daniele B, Rimassa L. Atezolizumab plus bevacizumab as first-line treatment of unresectable hepatocellular carcinoma: interim analysis results from the phase IIIb AMETHISTA trial. ESMO Open. 2025 Feb;10(2):104110. doi: 10.1016/j.esmoop.2024.104110. Epub 2025 Jan 27.

  PMID: 39874903 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

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 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: July 27, 2020
• Study Start: August 25, 2020
• Primary Completion: August 13, 2024
• Study Completion: August 13, 2024
• Last Updated: September 22, 2025
• Results First Posted: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

IT (21)