A Study of Atezolizumab (Anti-PD-L1 Antibody) plus Bevacizumab versus Active Surveillance as Adjuvant Therapy in Patients with Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Nov 2019 → ongoing

Decision date (initial)

2024-07-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-504303-86-00

EudraCT number

2019-002491-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Efficacy, Safety

To evaluate the efficacy of atezolizumab plus bevacizumab compared with active surveillance on the basis of recurrence-free survival (RFS) as determined by an IRF

Secondary objectives 4

1. To evaluate the efficacy of atezolizumab plus bevacizumab compared with active surveillance on the basis of overall survival (OS), RFS after randomization as determined by the investigator and by an Independent Review Facility (IRF), time to recurrence (TTR), IRF-assessed RFS and investigator-assessed RFS rate after randomization and OS rate at 24 months and 36 months, Time to extrahepatic spread or macrovascular invasion after randomization
2. To evaluate the safety of atezolizumab plus bevacizumab compared with active surveillance
3. To characterize the PK profile of atezolizumab when given in combination with bevacizumab
4. To evaluate the immune response to atezolizumab

Conditions and MedDRA coding

High-risk hepatocellular carcinoma (HCC)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participants with a first diagnosis of HCC who have undergone either curative resection or ablation (RFS or MWA only) within 4-12 weeks prior to randomization
2. High risk for HCC recurrence after resection or ablation
3. Full recovery from surgical resection or ablation within 4 weeks prior to randomization
4. Absence of MVI (Vp3 or Vp4)
5. ECOG Performance Status of 0 or 1
6. Child-Pugh Class A status

Exclusion criteria 6

1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
2. Evidence of residual, recurrent, or metastatic disease at randomization
3. On the waiting list for liver transplant
4. History of hepatic encephalopathy
5. Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization
6. Have received more than 1 cycle of adjuvant TACE following surgical resection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Independent Review Facility (IRF)-assessed recurrence-free survival (RFS)

Secondary endpoints 12

1. 1. Overall Survival (OS) rate at 24 months and 36 months
2. 2. OS
3. 3. RFS as determined by the investigator
4. 4. Time to Recurrence (TTR)
5. 5. Time to extrahepatic spread (EHS) or macrovascular invasion
6. 6. RFS after randomization as determined by the investigator and by an IRF, among patients in the PD-L1-high subgroup
7. 7. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0
8. 8. Change from baseline in targeted vital signs
9. 9. Change from baseline in targeted clinical laboratory test results
10. 10. Serum concentration of atezolizumab at specified timepoints
11. 11. Prevalence of anti-drug antibody (ADAs) to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study
12. 12. IRF-assessed RFS and investigator-assessed RFS rate at 24 and 36 months after randomization

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 11

Locations

9 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 102 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications