An Investigational Immuno-therapy Study of Nivolumab Compared to Sorafenib as a First Treatment in Patients With Advanced Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

A Randomized, Multi-center Phase III Study of Nivolumab Versus Sorafenib as First-Line Treatment in Patients With Advanced Hepatocellular Carcinoma (CheckMate 459: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 459)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02576509
• Other study ID #: CA209-459
• Status: Completed
• Phase: Phase 3
• Start date: December 7, 2015
• Est. completion date: February 7, 2024

Study information

• Verified date: March 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 743
• Est. completion date: February 7, 2024
• Est. primary completion date: May 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Nivolumab
Specified Dose on Specified Days
• Sorafenib
Specified Dose on Specified Days

Locations

Country	Name	City	State
Australia	Local Institution - 0007	Adelaide	South Australia
Australia	Local Institution - 0005	Camperdown	New South Wales
Australia	Local Institution - 0001	Clayton	Victoria
Australia	Local Institution - 0002	Heidelberg	Victoria
Australia	Local Institution - 0008	Nedlands	Western Australia
Australia	Local Institution - 0003	Prahran	Victoria
Austria	Local Institution - 0039	Graz
Austria	Local Institution - 0038	Wien
Belgium	Local Institution - 0075	Bruxelles
Belgium	Local Institution - 0091	Leuven
Belgium	Local Institution - 0077	Liege
Canada	Local Institution - 0043	Calgary	Alberta
Canada	Local Institution - 0042	Quebec
Canada	Local Institution - 0044	Vancouver	British Columbia
China	Local Institution - 0137	Beijing	Beijing
China	Local Institution - 0139	Beijing	Beijing
China	Local Institution - 0140	Beijing	Beijing
China	Local Institution - 0141	Beijing	Beijing
China	Local Institution - 0136	Changchun	Jilin
China	Local Institution - 0163	Changchun	Jilin
China	Local Institution - 0148	Changsha	Hunan
China	Local Institution - 0162	Changsha	Hunan
China	Local Institution - 0169	Changzhou	Jiangsu
China	Local Institution - 0166	Dalian	Liaoning
China	Local Institution - 0152	Fuzhou	Fujian
China	Local Institution - 0144	Guangzhou	Guangdong
China	Local Institution - 0157	Guangzhou	Guangdong
China	Local Institution - 0161	Guangzhou	Guangdong
China	Local Institution - 0146	Hangzhou	Zhejiang
China	Local Institution - 0173	Hangzhou	Zhejiang
China	Local Institution - 0142	Harbin	Heilongjiang
China	Local Institution - 0164	Hefei	Anhui
China	Local Institution - 0135	Nanjing	Jiangsu
China	Local Institution - 0158	Nanning	Guangxi
China	Local Institution - 0145	Shanghai	Shanghai
China	Local Institution - 0151	Shanghai	Shanghai
China	Local Institution - 0159	Tianjin	Tianjin
China	Local Institution - 0138	Xi'an	Shan3xi
Czechia	Local Institution - 0029	Brno
Czechia	Local Institution - 0027	Hradec Kralove
Czechia	Local Institution - 0028	Olomouc
France	Local Institution - 0071	La Tronche
France	Local Institution - 0072	Lille Cedex
France	Local Institution - 0069	Lyon
France	Local Institution - 0073	Montpellier Cedex
France	Local Institution - 0067	Paris Cedex 13
France	Local Institution - 0068	Pessac
France	Local Institution - 0070	Rennes Cedex
France	Local Institution - 0074	Toulouse Cedex 9
Germany	Local Institution - 0036	Berlin
Germany	Local Institution - 0037	Essen
Germany	Local Institution - 0167	Frankfurt
Germany	Local Institution - 0034	Hamburg
Germany	Local Institution - 0031	Leipzig
Germany	Local Institution - 0035	Mainz
Germany	Local Institution - 0033	Munich
Germany	Local Institution - 0032	Regensburg
Germany	Local Institution - 0030	Tuebingen
Hong Kong	Local Institution - 0011	Hong Kong
Hong Kong	Local Institution - 0012	Hong Kong
Israel	Local Institution - 0082	Haifa
Israel	Local Institution - 0060	Jerusalem
Israel	Local Institution - 0058	Petah-tikva
Israel	Local Institution - 0059	Tel Aviv
Italy	Local Institution - 0054	Benevento
Italy	Local Institution - 0062	Bergamo
Italy	Local Institution - 0055	Milan
Italy	Local Institution - 0063	Orbassano
Italy	Local Institution - 0064	Siena
Japan	Local Institution - 0100	Chiba City	Chiba
Japan	Local Institution - 0131	Chiyoda-ku	Tokyo
Japan	Local Institution - 0101	Hiroshima
Japan	Local Institution - 0105	Kanazawa-shi	Ishikawa
Japan	Local Institution - 0110	Kawasaki-shi	Kanagawa
Japan	Local Institution - 0107	Kurume-shi	Fukuoka
Japan	Local Institution - 0111	Kyoto-shi	Kyoto
Japan	Local Institution - 0103	Matsuyama-shi	Ehime
Japan	Local Institution - 0114	Mitaka-shi	Tokyo
Japan	Local Institution - 0108	Musashino-shi	Tokyo
Japan	Local Institution - 0127	Ogaki-shi	Gifu
Japan	Local Institution - 0106	Osaka-Sayama-Shi	Osaka
Japan	Local Institution - 0115	Saga-shi	Saga
Japan	Local Institution - 0102	Sapporo-shi	Hokkaido
Japan	Local Institution - 0130	Sapporo-shi	Hokkaido
Japan	Local Institution - 0126	Shinjuku-ku	Tokyo
Japan	Local Institution - 0113	Suita	Osaka
Japan	Local Institution - 0104	Yokohama-shi	Kanagawa
Japan	Local Institution - 0112	Yokohama-shi	Kanagawa
Korea, Republic of	Local Institution - 0125	Daegu
Korea, Republic of	Local Institution - 0116	Goyang-si
Korea, Republic of	Local Institution - 0118	Jeollanam-do
Korea, Republic of	Local Institution - 0117	Seoul	Seocho-gu
Korea, Republic of	Local Institution - 0122	Seoul
Korea, Republic of	Local Institution - 0123	Seoul
Korea, Republic of	Local Institution - 0124	Seoul
Korea, Republic of	Local Institution - 0119	Seoul-si
Poland	Local Institution - 0023	Gdansk
Poland	Local Institution - 0056	Warszawa
Poland	Local Institution - 0045	Wroclaw
Russian Federation	Local Institution - 0096	Moscow
Singapore	Local Institution - 0013	Singapore
Singapore	Local Institution - 0014	Singapore
Spain	Local Institution - 0065	Alicante
Spain	Local Institution - 0085	Majadahonda - Madrid
Spain	Local Institution - 0009	Pamplona
Spain	Local Institution - 0010	Santiago Compostela
Sweden	Local Institution - 0088	Goteborg
Sweden	Local Institution - 0087	Stockholm
Switzerland	Local Institution - 0040	Basel
Switzerland	Local Institution - 0041	Bern
Taiwan	Local Institution - 0129	Kaohsiung County
Taiwan	Local Institution - 0133	Taichung
Taiwan	Local Institution - 0121	Tainan
Taiwan	Local Institution - 0132	Tainan
Taiwan	Local Institution - 0099	Taipei
Taiwan	Local Institution - 0120	Taipei
Taiwan	Local Institution - 0128	Taoyuan County
United Kingdom	Local Institution - 0079	Glasgow	Lanarkshire
United Kingdom	Local Institution - 0081	Liverpool
United Kingdom	Local Institution - 0078	London	Greater London
United Kingdom	Local Institution - 0080	London	Greater London
United States	Local Institution - 0066	Birmingham	Alabama
United States	Local Institution - 0016	Charlotte	North Carolina
United States	Local Institution - 0061	Chicago	Illinois
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Local Institution - 0020	Los Angeles	California
United States	Local Institution - 0050	Madison	Wisconsin
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Local Institution - 0083	New York	New York
United States	Local Institution - 0093	New York	New York
United States	Local Institution - 0019	Philadelphia	Pennsylvania
United States	Local Institution - 0095	Philadelphia	Pennsylvania
United States	Local Institution - 0017	San Antonio	Texas
United States	Local Institution - 0015	San Francisco	California
United States	Local Institution - 0084	San Francisco	California
United States	Local Institution - 0026	Seattle	Washington
United States	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington
United States	Scott & White Memorial Hospital And Clinic	Temple	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  Czechia,  France,  Germany,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  Singapore,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	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.	time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months)
Secondary	Objective Response Rate (ORR) Per BICR RECIST 1.1	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	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)
Secondary	Progression-Free Survival (PFS)	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.	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)
Secondary	Efficacy Based on PD-L1 Expression - OS and PFS	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.	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)
Secondary	Efficacy Based on PD-L1 Expression - ORR	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.	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)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting