Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202402574273311 Date of Registration: 01/02/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152/SKYSCRAPER-14)
Official scientific title A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
Brief summary describing the background and objectives of the trial The purpose of this study is to assess the efficacy and safety of tiragolumab, an anti-TIGIT monoclonal antibody, when administered in combination with atezolizumab and bevacizumab as first-line treatment, in participants with unresectable, locally advanced or metastatic hepatocellular carcinoma (HCC). Despite recent advances in the first-line treatment setting for patients with HCC, notably cancer immunotherapy (CIT)-based combination regimens, there remains a need for novel therapeutic approaches that target mechanisms of resistance to CIT and provide more durable clinical benefit and improve long-term survival outcomes. TIGIT is believed to play an important role in HCC pathogenesis and resistance to PD-1/PD-L1 blockade. The addition of tiragolumab to atezolizumab plus bevacizumab may augment anticancer immunity, thereby improving clinical outcomes.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Cancer
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 30/04/2024
Actual trial start date
Anticipated date of last follow up 01/09/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 650
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Atezolizumab plus Bevacizumab plus Tiragolumab Atezolizumab (Tecentriq) - Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle. Bevacizumab (Avastin) - Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle. Tiragolumab (MTIG7192A) - Tiragolumab will be administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle. Atezolizumab plus bevacizumab plus tiragolumab will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Atezolizumab plus bevacizumab plus tiragolumab will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. 325
Control Group Atezolizumab plus Bevacizumab plus Placebo Atezolizumab (Tecentriq) - Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle. Bevacizumab (Avastin) - Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle. Placebo - matching tiragolumab will be administered by IV infusion on Day 1 of each 21-day cycle. Atezolizumab, bevacizumab plus placebo will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Atezolizumab, bevacizumab plus placebo will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. 325 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants Disease that is not amenable to curative surgical and/or locoregional therapies No prior systemic treatment for locally advanced or metastatic and/or unresectable HCC Measurable disease according to RECIST v1.1 ECOG Performance Status of 0 or 1 within 7 days prior to randomization Child-Pugh Class A within 7 days prior to randomization Adequate hematologic and end-organ function Female participants of childbearing potential must be willing to avoid pregnancy within 5 months after the final dose of atezolizumab, within 6 months after the final dose of bevacizumab, and within 90 days after the final dose of tiragolumab/placebo Male participants with a female partner of childbearing potential or pregnant female partner must remain abstinent or use a condom during the treatment period and for 6 months after the final dose of bevacizumab and for 90 days after the final dose of tiragolumab/placebo to avoid exposing the embryo. Pregnancy or breastfeeding within 5 months after the final dose of atezolizumab, within 6 months after the final dose of bevacizumab, and within 90 days after the final dose of tiragolumab/placebo Prior treatment with CD137 agonists or immune checkpoint blockade therapies Treatment with investigational therapy within 28 days prior to initiation of study treatment Treatment with locoregional therapy to liver within 28 days prior to initiation of study treatment, or non-recovery from side effects of any such procedure Treatment with systemic immunostimulatory agents Treatment with systemic immunosuppressive medication 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 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 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 Mixed histology or other subtypes/variants of HCC, including, but not limited to, known liver adenocarcinoma, fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) Acute Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. 80 and over: 80+ Year,Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 20/12/2023 Kenyatta National Hospital University of Nairobi
Ethics Committee Address
Street address City Postal code Country
Nairobi Nairobi 00202 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Investigator-Assessed Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first.
Primary Outcome Overall Survival (OS) From randomization to death from any cause
Secondary Outcome Investigator-Assessed Confirmed Objective Response Rate (ORR) According to RECIST v1.1 From randomization up to approximately 36 months
Secondary Outcome Investigator-Assessed Duration of Objective Response (DOR) According to RECIST v1.1 From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first
Secondary Outcome Investigator-Assessed PFS Rate According to RECIST v1.1 at 6 and 12 Months Month 6, Month 12
Secondary Outcome Investigator-Assessed PFS According to Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first
Secondary Outcome Investigator-Assessed Confirmed ORR According to HCC mRECIST From randomization up to approximately 36 months
Secondary Outcome Investigator-Assessed DOR According to HCC mRECIST From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first
Secondary Outcome Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer 30 (QLQ-C30) Subscales From randomization up to approximately 36 months
Secondary Outcome Change from Baseline in GHS/QoL, Physical Functioning, and Role Functioning Assessed Using the EORTC QLQ-C30 From baseline up to approximately 36 months
Secondary Outcome Percentage of Participants With Adverse Events Up to approximately 36 months
Secondary Outcome Serum Concentrations of Atezolizumab Prior to the first infusion and 30 minutes after atezolizumab infusion on Day 1 of Cycle 1, prior to infusion on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation
Secondary Outcome Serum Concentrations of Tiragolumab Prior to the first infusion and 30 minutes after tiragolumab infusion on Day 1 of Cycle 1, prior to infusion on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit
Secondary Outcome Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit
Secondary Outcome Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University of Nairobi Institute of Tropical and Infectious Diseases P.O. BOX 19676-00202 Nairobi 00202 Kenya
Uganda Cancer Institute Upper Mulago Hill Kampala Uganda
Sweden Ghana Medical Center East Legon Hills, Katamanso near Nmai Djorm, East Legon Accra Ghana
Korle Bu Teaching Hospital Korle Bu Teaching Hospital, Department of Surgery, Guggisberg Avenue Accra Ghana
FUNDING SOURCES
Name of source Street address City Postal code Country
Roche The Atrium, 6th Floor Chaka Road, off Lenana Road Nairobi 00100 Kenya
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Roche The Atrium, 6th Floor Chaka Road, off Lenana Road Nairobi 00100 Kenya Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Arpna Patel arpna.patel@roche.com +441707366419 Falcon Way
City Postal code Country Position/Affiliation
Welwyn Garden City al73pw United Kingdom Clinical Operations Lead
Role Name Email Phone Street address
Principal Investigator Njoki Njiraini pnjokinjiraini@gmail.com 254717333452 P.O.BOX 19676 00200 NAIROBI
City Postal code Country Position/Affiliation
Nairobi 0020 Kenya Consultant Clinical Oncologist
Role Name Email Phone Street address
Scientific Enquiries Christopher Cotter cotterc1@gene.com +16313831379 1 DNA Way South San Francisco
City Postal code Country Position/Affiliation
San Francisco 94080 United States of America Senior Clinical Scientist
Role Name Email Phone Street address
Principal Investigator Fred Okuku machyokuku2001@yahoo.com +256772485172 Upper Mulago Hill
City Postal code Country Position/Affiliation
Kampala Uganda Principal Investigator
Role Name Email Phone Street address
Principal Investigator Emmanual Amankwaa Frempong emmanuel.frempong@sgmcltd.com +233547478766 Sweden Ghana Medical Center, East Legon Hills, Katamanso, Near Nmai Djorm
City Postal code Country Position/Affiliation
Accra Ghana Principal Investigator
Role Name Email Phone Street address
Principal Investigator Asare Kwaku Offei asareoffei@gmail.com +233244871291 Korle Bu Teaching Hospital, Department of Surgery, Guggisberg Avenue
City Postal code Country Position/Affiliation
Accra Ghana Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm). Clinical Study Report,Statistical Analysis Plan,Study Protocol After the medicine studied has been approved by regulators for the indication in both the US and EU or terminated from development (all indications) 18 months after completion of the study report( to enable a publication to be submitted) Available studies are listed and available on the Vivli platform. Data requestors should use the Vivli data request form to request companies data Package(s). If approved requestors will need to sign a Data Use Agreement and the anonymized data will be shared in the Vivli secure research environment.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://vivli.org/ourmember/roche/ No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information