A Study of Relatlimab in Combination With Nivolumab in Participants With Advanced Liver Cancer Who Have Never Been Treated With Immuno-oncology Therapy After Prior Treatment With Tyrosine Kinase Inhibitors

A Phase 2, Randomized, Open-label Study of Relatlimab in Combination With Nivolumab in Participants With Advanced Hepatocellular Carcinoma Who Are Naive to IO Therapy But Progressed on Tyrosine Kinase Inhibitors (RELATIVITY-073)

The purpose of this study is to evaluate the effectiveness and safety of relatlimab in combination with nivolumab in participants with advanced liver cancer who have never been treated with immuno-oncology therapy, after prior treatment with tyrosine kinase inhibitor therapy.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma; Hepatoma; Liver Cell Carcinoma; Liver Cancer, Adult; Liver Cell Carcinoma, Adult
• Intervention / Treatment: Biological: Nivolumab; Biological: Relatlimab

• Study Type: Interventional
• Enrollment (Actual): 266
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, 1181
      • Local Institution - 0010
  • Distrito Federal
    • Buenos Aires, Distrito Federal, Argentina, C1096AAS
      • Local Institution - 0019
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2002KDS
      • Local Institution - 0017
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, 4000
      • Local Institution - 0063
• Brazil
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-090
      • Local Institution - 0025
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Local Institution - 0060
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784400
      • Local Institution - 0016
    • Ribeirão Preto, São Paulo, Brazil, 14051-140
      • Unidade de Pesquisa Clínica do Hospital da Clínicas de Ribeirão Preto-Clinical Oncology
    • São Paulo, São Paulo, Brazil, 01246-000
      • Local Institution - 0015
• Chile
  • Región de la Araucanía
    • Temuco, Región de la Araucanía, Chile, 4800827
      • Local Institution - 0024
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 000000
      • Local Institution - 0029
    • Santiago, Santiago Metropolitan, Chile, 8420383
      • Local Institution - 0018
• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Local Institution - 0113
  • Hunan
    • Changsha, Hunan, China, 410013
      • Local Institution - 0114
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Local Institution - 0118
  • Shan3xi
    • Xi'an, Shan3xi, China, 710126
      • Local Institution - 0108
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Local Institution - 0107
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Local Institution - 0117
• Czechia
  • Brno, Czechia, 65653
    • Local Institution - 0048
  • Hradec Králové, Czechia, 50005
    • Local Institution - 0047
  • Prague, Czechia, 140 59
    • Local Institution - 0046
• France
  • Clichy, France, 92110
    • Local Institution - 0068
  • Grenoble, France, 38043
    • Local Institution - 0105
  • Lyon, France, 69004
    • Local Institution - 0074
  • Pessac, France, 33600
    • Local Institution - 0067
  • Meurthe-et-Moselle
    • Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France, 54511
      • Local Institution - 0069
• Hong Kong
  • Hksar, Hong Kong
    • Local Institution - 0077
  • Shatin, Hong Kong
    • Local Institution - 0079
• Japan
  • Ishikawa, Japan, 920-8641
    • Local Institution - 0075
  • Kyoto, Japan, 602-8566
    • Local Institution - 0071
  • Ehime
    • Matsuyama, Ehime, Japan, 790-0024
      • Local Institution - 0072
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 232-0024
      • Local Institution - 0054
    • Yokohama, Kanagawa, Japan, 241-8515
      • Local Institution - 0076
  • Osaka
    • Ōsaka-sayama, Osaka, Japan, 589-8511
      • Local Institution - 0045
• Mexico
  • Cuauhtémoc, Mexico, 06700
    • Local Institution - 0100
  • Oaxaca City, Mexico, 68020
    • Local Institution - 0106
  • San Luis Potosí
    • San Luis Potosí City, San Luis Potosí, Mexico, 78250
      • Local Institution - 0101
• New Zealand
  • Auckland, New Zealand, 1023
    • Local Institution - 0003
• Poland
  • Bytom, Poland, 41-900
    • Local Institution - 0012
  • Mysowice, Poland, 41-400
    • Local Institution - 0009
  • Warsaw, Poland, 02-034
    • Local Institution - 0039
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-501
      • Local Institution - 0013
• Romania
  • Bucharest, Romania, 022328
    • Local Institution - 0037
  • Cluj-Napoca, Romania, 400015
    • Local Institution - 0036
  • Suceava, Romania, 720214
    • Local Institution - 0070
  • Dolj
    • Craiova, Dolj, Romania, 200542
      • Local Institution - 0038
• Singapore
  • Singapore, Singapore, 308433
    • Local Institution - 0004
  • Central Singapore
    • Singapore, Central Singapore, Singapore, 168583
      • Local Institution - 0001
• South Korea
  • Seongnam-si, South Korea, 13496
    • Local Institution - 0020
  • Seoul, South Korea, 06351
    • Local Institution - 0043
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, South Korea, 05505
      • Local Institution - 0011
• Spain
  • Barcelona, Spain, 08036
    • Local Institution - 0066
  • Córdoba, Spain, 14004
    • Local Institution - 0073
  • Madrid, Spain, 28009
    • Local Institution - 0051
  • Madrid, Spain, 28041
    • Local Institution - 0049
  • Pamplona, Spain, 31008
    • Local Institution - 0058
  • Gipuzkoa
    • Donostia / San Sebastian, Gipuzkoa, Spain, 20014
      • Local Institution - 0050
• Taiwan
  • Taichung, Taiwan, 40447
    • Local Institution - 0041
  • Tainan, Taiwan, 704
    • Local Institution - 0034
  • Taipei, Taiwan, 11217
    • Local Institution - 0042
  • Taipei, Taiwan, 100
    • Local Institution - 0031
  • Taoyuan District, Taiwan, 333
    • Local Institution - 0032
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Local Institution - 0089
  • Edirne, Turkey (Türkiye), 22030
    • Local Institution - 0090
  • Kadiköy/Istanbul, Turkey (Türkiye), 41380
    • Local Institution - 0091

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Must have a diagnosis of hepatocellular carcinoma (HCC) based on histological confirmation
• Must have advanced/metastatic HCC
• Have to be immunotherapy treatment-naive in the advanced/metastatic setting
• Must have at least one Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 measurable untreated lesion
• Child-Pugh score of 5 or 6
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 for ECOG performance status scale

Key Exclusion Criteria:

• Known fibrolamellar HCC, sarcomatoid HCC, combined hepatocellular cholangiocarcinoma
• Prior organ allograft or allogeneic bone marrow transplantation
• No uncontrolled or significant cardiovascular disease
• No active known autoimmune disease
• Have received one or two lines of tyrosine kinase inhibitor therapies
• Evidence of radiographic progression on or after the last line of tyrosine kinase inhibitor therapy

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A : Nivolumab	Biological: Nivolumab; Specified dose on specified days; Other Names: OPDIVO, BMS-936558
Experimental: Arm B : Nivolumab + Relatlimab Dose 1	Biological: Nivolumab; Specified dose on specified days; Other Names: OPDIVO, BMS-936558; Biological: Relatlimab; Specified dose on specified days; Other Names: BMS-986016
Experimental: Arm C : Nivolumab + Relatlimab Dose 2	Biological: Nivolumab; Specified dose on specified days; Other Names: OPDIVO, BMS-936558; Biological: Relatlimab; Specified dose on specified days; Other Names: BMS-986016

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate(ORR) Assessed by BICR	Objective Response Rate (ORR) (as per Recists v1.1) is defined as the percentage of participants whose best overall response (BOR) is either confirmed complete response (CR) or confirmed partial response (PR) based on BICR assessments among all participants in the respective analysis set. BOR is defined as the best response, as determined by the BICR, recorded between the date of randomization and the date of first objectively documented progression or death due to any cause or the date of subsequent therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR determination. Confirmation of response is required at least 4 weeks after the initial response.	From randomization to primary completion date (Approximately 29.5 Months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate Assessed by BICR	Disease Control Rate (DCR) (as per Recists v1.1) is defined as the number of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants.	From randomization to primary completion date (Approximately 29.5 Months)
Duration of Response Assessed by BICR	Duration of Response (DOR) (as per Recists v1.1) is defined as the time between the date of first documented response (CR or PR) that is subsequently confirmed, to the date of the first objectively documented tumor progression as determined by the BICR, or death due to any cause, whichever occurs first. Participants who die without a reported prior progression will be considered to have an event on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. DOR will be evaluated for responders (confirmed CR or PR) only.	From randomization to primary completion date (Approximately 29.5 Months)
Progression Free Survival(PFS) Assessed by BICR	PFS (as per Recists v1.1) is defined as the time between the date of randomization and the date of first documented tumor progression or death due to any cause, whichever occurs first. Participants who die without a reported progression will be considered to have progressed on the date of their death.	From randomization to primary completion date (Approximately 29.5 Months)
Objective Response Rate Assessed by Investigator	Objective Response Rate (ORR) (as per Recists v1.1) is defined as the percentage of participants whose best overall response (BOR) is either confirmed complete response (CR) or confirmed partial response (PR) based on investigator assessments among all participants in the respective analysis set. BOR is defined as the best response, as determined by the investigator, recorded between the date of randomization and the date of first objectively documented progression or death due to any cause or the date of subsequent therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR determination. Confirmation of response is required at least 4 weeks after the initial response.	From randomization to primary completion date (Approximately 29.5 Months)
Disease Control Rate Assessed by Investigator	Disease Control Rate (DCR) (as per Recists v1.1) is defined as the number of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants.	From randomization to primary completion date (Approximately 29.5 Months)
Duration of Response Assessed by Investigator	Duration of Response (DOR) (as per Recists v1.1) is defined as the time between the date of first documented response (CR or PR) that is subsequently confirmed, to the date of the first objectively documented tumor progression as determined by the investigator, or death due to any cause, whichever occurs first. Participants who die without a reported prior progression will be considered to have an event on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. DOR will be evaluated for responders (confirmed CR or PR) only.	From randomization to primary completion date (Approximately 29.5 Months)
Progression Free Survival(PFS) Assessed by Investigator	PFS (as per Recists v1.1) is defined as the time between the date of randomization and the date of first documented tumor progression or death due to any cause, whichever occurs first. Participants who die without a reported progression will be considered to have progressed on the date of their death.	From randomization to primary completion date (Approximately 29.5 Months)
Overall Survival (OS)	Overall survival (OS) is defined as the time from randomization to the date of death from any cause. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up.	From randomization to primary completion date (Approximately 29.5 Months)
Number of Participants With Adverse Events	Number of participants with an Adverse Event. An Adverse Event is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.	From randomization to primary completion date (Approximately 29.5 Months). Includes events reported between first dose and 30 days after last dose of study therapy.
Number of Participants With Serious Adverse Events	Number of participants with Serious Adverse Events A serious adverse event is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event.	From randomization to primary completion date (Approximately 29.5 Months). Includes events reported between first dose and 30 days after last dose of study therapy.
Number of Participants With Adverse Events Leading to Discontinuation	Number of participants with Adverse Events Leading to Discontinuation	From randomization to primary completion date (Approximately 29.5 Months). Includes events reported between first dose and 30 days after last dose of study therapy.
Death Summary	Number of participants who died.	From randomization to primary completion date (Approximately 29.5 Months)
Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests	Number of participants with clinical laboratory abnormalities in specific liver tests	From randomization to primary completion date (Approximately 29.5 Months). Includes events reported between first dose and 30 days after last dose of study therapy.
Number of Participants With Clinical Laboratory Abnormalities in Thyroid Tests	Number of participants with clinical laboratory abnormalities in thyroid tests	From randomization to primary completion date (Approximately 29.5 Months). Includes events reported between first dose and 30 days after last dose of study therapy.

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): November 19, 2025

Study Registration Dates

• First Submitted: September 24, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Estimated): January 8, 2026
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Liver Cancer; Advanced Hepatocellular Carcinoma; Liver Cancer, Adult; Liver Cell Carcinoma; Liver Cell Carcinoma, Adult
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; relatlimab
• Other Study ID Numbers: CA224-073; 2018-003151-38 (EudraCT Number); U1111-1218-6499 (Other Identifier: UTN Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes