A Study of Atezolizumab with Lenvatinib or Sorafenib versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated with Atezolizumab and Bevacizumab

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

6 May 2021 → ongoing

Decision date (initial)

2024-02-26

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

2023-503229-21-00

EudraCT number

2020-005231-78

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

-To evaluate the efficacy of atezolizumab plus lenvatinib or sorafenib compared with lenvatinib or sorafenib alone, on basis of the overall survival (OS)

Secondary objectives 5

1. - To evaluate the efficacy of atezolizumab plus lenvatinib or sorafenib compared with lenvatinib or sorafenib alone, based on progression free survival (PFS), confirmed objective response rate (ORR), time to progression (TTP) and duration of response (DOR), time to confirmed deterioration (TTCD), of health-related quality of life (HRQoL)
2. -To evaluate patient-reported function and general health status/quality of life (GHS/QoL) experienced by patients receiving atezolizumab plus lenvatinib or sorafenib versus lenvatinib or sorafenib alone
3. -To evaluate the safety of atezolizumab plus lenvatinib or sorafenib compared with lenvatinib or sorafenib alone, based on Incidence and severity of adverse events, Vital signs, Clinical laboratory test results
4. -To characterize the pharmacokinetic (PK) profile of atezolizumab when given in combination with lenvatinib or sorafenib
5. -To evaluate the immune response to atezolizumab

Conditions and MedDRA coding

Unresectable hepatocellular carcinoma (HCC)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. - 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 patients
2. Patients without cirrhosis require histological confirmation of diagnosis. HCC must be unamenable to curative surgical and/or locoregional therapies, or have progressed after surgical and /or locoregional therapies
3. Eastern Cooperative Oncology Group Performance Status of 0 or 1 within 7 days prior to randomization
4. Child-Pugh class A within 7 days prior to randomization
5. Life expectancy of at least 12 weeks
6. Patients with active hepatitis B virus (HBV) must have HBV deoxyribonucleic acid (DNA) < 500 international units per milliliter (IU/mL) obtained within 28 days prior to initiation of study treatment and received anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study

Exclusion criteria 6

1. Symptomatic, untreated, or actively progressing central nervous system metastases
2. History of leptomeningeal disease and hepatic encephalopathy
3. History of malignancy other than HCC within 5 years prior to screening
4. Significant cardiovascular disease within 3 months prior to initiation of study treatment
5. Known allergy or hypersensitivity to any of the investigational medicinal product (IMPs) or constituents of the products
6. Treatment with an investigational therapy within 28 days prior to initiation of study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1.OS, defined as the time from randomization into the study to death from any cause

Secondary endpoints 12

1. 1.PFS, defined as the time from randomization into the study to the first occurrence of disease progression or death from any cause
2. 2.ORR, defined as the proportion of patients with a best response of either complete or partial response
3. 3.TTP, defined as the time from randomization to the first occurrence of disease progression
4. 4.DOR, defined as the time from the first occurrence of a documented confirmed objective response to disease progression or death from any cause
5. 5. Time to confirmed deterioration (TCTD), of health-related quality of life (HRQoL), defined as the time from randomization to first confirmed deterioration
6. 6.Incidence and severity of adverse events (AEs), with severity determined according to national cancer institute common terminology criteria for adverse events version 5.0 (NCI CTCAE v5.0)
7. 7. Incidence and severity of AEs, including adverse events for combination treatment, AEs related against atezolizumab and tyrosine kinase inhibitor (TKI)-related AEs according to (NCI CTCAE v5.0)
8. 8.Incidence of vital sign abnormalities
9. 9.Incidence of clinical laboratory abnormalities
10. 10.Serum concentration of atezolizumab at specified timepoints
11. 11.Prevalence of anti-drug antibodies (ADAs) against atezolizumab at time of study entry
12. 12.Incidence of ADAs against atezolizumab during the study

Investigational products

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

Test 1

Comparator 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 8

Locations

12 EU/EEA countries · 62 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 119 files

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

Application history

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