eligibility Criteria: Inclusion Criteria: * Histologically confirmed advanced hepatocellular carcinoma, not eligible for surgical and/or locoregional therapies; or progressive disease after surgical and /or locoregional therapies * Locoregional therapy for hepatocellular carcinoma (HCC) must be completed at least 4 weeks prior to the baseline scan * Child-Pugh Class A * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 Exclusion Criteria: * Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC * Prior liver transplant * Active, known, or suspected autoimmune disease Other protocol-defined inclusion/exclusion criteria apply
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Nivolumab specified dose on specified days
intervention Names
Drug: Nivolumab
label
Nivolumab
type
EXPERIMENTAL
description
Sorafenib specified dose on specified days
intervention Names
Drug: Sorafenib
label
Sorafenib
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Nivolumab
description
Specified Dose on Specified Days
name
Nivolumab
type
DRUG
arm Group Labels
Sorafenib
description
Specified Dose on Specified Days
name
Sorafenib
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 743
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
OS is defined as the time from the date of randomization to the date of death due to any cause in all randomized participants. Participants who are alive will be censored at the last known alive dates. Based on Kaplan-Meier Estimates.
measure
Overall Survival (OS)
time Frame
time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months)

secondary Outcomes

description
ORR is defined as the proportion of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR is defined as the best response designation, as determined based on BICR-assessed tumor response according to RECIST 1.1, recorded between the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent anti-cancer therapy, all available response designations will contribute to the BOR determination. For a BOR of CR or PR, the initial response assessment must be confirmed by a consecutive assessment no less than 4 weeks (28 days) later. Estimate of (Nivolumab - Sorafenib) is based on CMH method of weighting, stratified by stratification factors
measure
Objective Response Rate (ORR) Per BICR RECIST 1.1
time Frame
the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)
description
PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by BICR according to RECIST 1.1 or death due to any cause in all randomized participants. Participants who die without a reported prior progression and without initiation of subsequent anti-cancer therapy will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment. Participants who did not have baseline tumor assessment will be censored on the date they were randomized. Participants who did not have any on study tumor assessments and did not die will be censored on the date they were randomized. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to subsequent anti-cancer therapy.
measure
Progression-Free Survival (PFS)
time Frame
time from the date of randomization to the date of the first objectively documented tumor progression or death, assessed up to May 2019 (approximately 40 months)
description
PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as: Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling. Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate). PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression: * PD-L1 \> X %: ≥ X % PD-L1 expression * PD-L1 \< X %: \< X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored. Confidence interval based on the Clopper and Pearson method.
measure
Efficacy Based on PD-L1 Expression - OS and PFS
time Frame
the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)
description
PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as: Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling. Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate). PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression: * PD-L1 \> X %: ≥ X % PD-L1 expression * PD-L1 \< X %: \< X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored. Confidence interval based on the Clopper and Pearson method.
measure
Efficacy Based on PD-L1 Expression - ORR
time Frame
the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)

Full study description

brief Summary: The purpose of this study is to determine if nivolumab or sorafenib is more effective in the treatment of Advanced Hepatocellular Carcinoma.

Source references

references

citation
Bitar R, Salem R, Finn R, Greten TF, Goldberg SN, Chapiro J. Interventional Oncology Meets Immuno-oncology: Combination Therapies for Hepatocellular Carcinoma. Radiology. 2024 Nov;313(2):e232875. doi: 10.1148/radiol.232875.
pmid
39560477
type
DERIVED
citation
Zhou X, Cao J, Topatana W, Xie T, Chen T, Hu J, Li S, Juengpanic S, Lu Z, Zhang B, Wang K, Feng X, Shen J, Chen M. Evaluation of PD-L1 as a biomarker for immunotherapy for hepatocellular carcinoma: systematic review and meta-analysis. Immunotherapy. 2023 Apr;15(5):353-365. doi: 10.2217/imt-2022-0168. Epub 2023 Feb 27.
pmid
36852452
type
DERIVED
citation
Li Y, Liang X, Li H, Chen X. Atezolizumab plus bevacizumab versus nivolumab as first-line treatment for advanced or unresectable hepatocellular carcinoma: A cost-effectiveness analysis. Cancer. 2022 Nov 15;128(22):3995-4003. doi: 10.1002/cncr.34457. Epub 2022 Sep 16.
pmid
36111952
type
DERIVED
citation
Shi J, Liu J, Tu X, Li B, Tong Z, Wang T, Zheng Y, Shi H, Zeng X, Chen W, Yin W, Fang W. Single-cell immune signature for detecting early-stage HCC and early assessing anti-PD-1 immunotherapy efficacy. J Immunother Cancer. 2022 Jan;10(1):e003133. doi: 10.1136/jitc-2021-003133.
pmid
35101942
type
DERIVED
citation
Yau T, Park JW, Finn RS, Cheng AL, Mathurin P, Edeline J, Kudo M, Harding JJ, Merle P, Rosmorduc O, Wyrwicz L, Schott E, Choo SP, Kelley RK, Sieghart W, Assenat E, Zaucha R, Furuse J, Abou-Alfa GK, El-Khoueiry AB, Melero I, Begic D, Chen G, Neely J, Wisniewski T, Tschaika M, Sangro B. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022 Jan;23(1):77-90. doi: 10.1016/S1470-2045(21)00604-5. Epub 2021 Dec 13.
pmid
34914889
type
DERIVED