Carcinoma, HepatocellularPhase 1/2RELATIVITY-106NCT05337137
A Study of Nivolumab and Relatlimab in Combination With Bevacizumab in Advanced Liver Cancer
A Phase 1/2 study testing Relatlimab, Nivolumab and Bevacizumab in people with Carcinoma, Hepatocellular, run by Bristol-Myers Squibb at 61 sites in 15 countries.
Trial summary
The purpose of this study is to evaluate the safety and effectiveness of triplet therapy of nivolumab, relatlimab and bevacizumab versus nivolumab and bevacizumab in participants with untreated advanced/metastatic hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Relatlimab, Nivolumab and Bevacizumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 61 sitesin 15 countries
- Study dates
- 5 May 2022to 18 Nov 2025
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed advanced/metastatic hepatocellular carcinoma (HCC)
- Naïve to systemic therapy for advanced/metastatic HCC (prior neo-adjuvant or adjuvant immunotherapy is permitted if recurrence occurs ≥ 6 months after treatment completion and the case is discussed with BMS medical team)
- Child-Pugh score of 5 or 6 (ie, Child-Pugh A)
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Who cannot join
- Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC
- Prior allogenic stem cell or solid organ transplantation
- Untreated symptomatic central nervous system (CNS) metastases
- Clinically significant ascites as defined by:
- Prior ascites that required treatment and requires on-going prophylaxis, or ii) Current ascites requiring treatment
- Other protocol-defined inclusion/exclusion criteria apply
Trial locations and contacts
61 sites in 15 countries.
61 sites in 15 countries
United States10 sites
Local Institution - 0059
Baltimore, Maryland, 21231
Local Institution - 0060
Boston, Massachusetts, 02114
Local Institution - 0065
Boston, Massachusetts, 02215
Local Institution - 0042
Los Angeles, California, 90033
Local Institution - 0039
Los Angeles, California, 90095
Local Institution - 0033
Milwaukee, Wisconsin, 53226
Local Institution - 0061
New York, New York, 10065
Local Institution - 0034
San Francisco, California, 94115
Local Institution - 0062
The Bronx, New York, 10461
Local Institution - 0030
Washington D.C., District of Columbia, 20007
France6 sites
Local Institution - 0021
Avignon, Cedex 9, 84918
Local Institution - 0012
Grenoble, 38043
Local Institution - 0001
Nice, 06202
Local Institution - 0002
Reims, 51092
Local Institution - 0008
Rennes, 35042
Local Institution - 0054
Suresnes, 92151
Japan6 sites
Local Institution - 0063
Chuo-ku, Tokyo, 104-0045
Local Institution - 0058
Kanazawa, Ishikawa-ken, 9208641
Local Institution - 0047
Kashiwa-shi, Chiba, 2778577
Local Institution - 0048
Matsuyama, Ehime, 7900024
Local Institution - 0041
Sayama, Osaka, 5898511
Local Institution - 0050
Yokohama, Kanagawa, 2320024
Spain6 sites
Local Institution - 0067
Madrid, Sede Madrid, 28027
Local Institution - 0053
Madrid, 28046
Local Institution - 0038
Pamplona, 31008
Local Institution - 0007
Santander, Cantabria, 39008
Local Institution - 0032
Santiago de Compostela, A Coruña, 15706
Local Institution - 0040
Zaragoza, 50009
Australia5 sites
Local Institution - 0022
Adelaide, South Australia, 5000
Local Institution - 0045
Camperdown, New South Wales, 2050
Local Institution - 0026
Heidelberg, Victoria, 3084
Local Institution - 0013
Melbourne, Victoria, 3065
Local Institution - 0017
Nedlands, Western Australia, 6009
Germany4 sites
Local Institution - 0051
Düsseldorf, North Rhine-Westphalia, 40225
Local Institution - 0035
Frankfurt, 60590
Local Institution - 0057
Mainz, 55131
Local Institution - 0055
Munich, 81377
Singapore4 sites
Local Institution - 0029
Singapore, 168583
Local Institution - 0027
Singapore, 217562
Local Institution - 0018
Singapore, 308433
Local Institution - 0044
Singapore, 329563
Taiwan4 sites
Local Institution - 0043
District Taichung City, Tai Zhong Shi, 404
Local Institution - 0024
Taichung, 40705
Local Institution - 0046
Taipei, 10048
Local Institution - 0049
Taipei, 11217
Italy3 sites
Local Institution - 0036
Milan, 20122
Local Institution - 0003
Padova, 35128
Local Institution - 0010
Roma, 00168
Poland3 sites
Local Institution - 0028
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796
Local Institution - 0023
Gdansk, 80-219
Local Institution - 0016
Warsaw, Masovian Voivodeship, 02-034
Canada2 sites
Local Institution - 0025
Edmonton, Alberta, T6G 1Z2
Local Institution - 0009
Toronto, Ontario, M5G 2M9
China2 sites
Local Institution - 0064
Guangzhou, Guangdong, 510515
Local Institution - 0066
Xi'an, Shan3xi, 710700
Hong Kong2 sites
Local Institution - 0004
Hong Kong, 0
Local Institution - 0031
Shatin, 999077
Puerto Rico2 sites
Local Institution - 0052
Rio Piedras, PR, 935
Local Institution - 0019
San Juan, 00927
South Korea2 sites
Local Institution - 0037
Seongnam-si, Gyeonggido, 13496
Local Institution - 0056
Seoul, 138-736
About this study
Official title: A Phase 1/2, Safety Confirmation, Placebo-controlled, Randomized Study of Nivolumab in Combination With Relatlimab and Bevacizumab in Treatment-naive Advanced/Metastatic Hepatocellular Carcinoma
The purpose of this study is to evaluate the safety and effectiveness of triplet therapy of nivolumab, relatlimab and bevacizumab versus nivolumab and bevacizumab in participants with untreated advanced/metastatic hepatocellular carcinoma (HCC).
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Relatlimab, Nivolumab, Bevacizumab, Placebo
- Keywords
- Hepatocellular Carcinoma, HCC, Liver Cancer, Relatlimab, Nivolumab, Bevacizumab, First line HCC
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RelatlimabDrug
Also called BMS-986016
Specified dose on specified days
NivolumabDrug
Also called BMS-936558, Opdivo
Specified dose on specified days
BevacizumabDrug
Also called Avastin
Specified dose on specified days
PlaceboOther
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Relatlimab + Nivolumab + Bevacizumab | Experimental | Not described Receives: Drug: Relatlimab; Drug: Nivolumab; Drug: Bevacizumab |
| Arm B: Placebo + Nivolumab + Bevacizumab | Experimental | Not described Receives: Drug: Nivolumab; Drug: Bevacizumab; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities
Bevacizumab DLTs: Include any AE causing >42-day delay, GI perforation, nephrotic syndrome, Grade 3/4 infusion reactions, Death events, neutropenic fever, most non-hematologic toxicities (with specified exceptions), prolonged severe GI/electrolyte issues, significant fatigue, severe liver enzyme elevation, PRES/RPLS, severe hypertension or cardiac events, thromboembolism, major bleeding, wound complications, fistula, necrotizing fasciitis, and severe hematologic toxicity.
Immunotherapy DLTs: Include severe immune-related events (eg, colitis, pneumonitis, uveitis), Grade 4 organ toxicities, serious hypersensitivity, prolonged/recurrent AEs, severe electrolyte/GI/fatigue events, Grade 5 events, severe hematologic, hepatic, neurologic, cardiac (myocarditis), and severe dermatologic reactions (eg, SJS/TEN, DRESS).
Measured: From Day 1 (first dose) untill 6 weeks post first dose
Objective Response Rate (ORR) Assessed by BICR - All Comer Population
Objective response rate (ORR) is defined as the percentage of participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on blinded independent central review (BICR) assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 3 years)
Objective Response Rate (ORR) Assessed by BICR - All EHSS No Population
Objective response rate (ORR) is defined as the percentage of participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on blinded independent central review (BICR) assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 3 years)
Secondary outcomes (7)
Progression-Free Survival (All Comer Population) Per BICR in Participants With LAG-3 Positive Status(≥1% by IHC)
Progression free survival (PFS) is defined as time from on treatment to disease progression or death (whichever comes first). Disease progression is defined as Unequivocal progression of existing non-target lesions.
Measured: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 3 years)
Progression-Free Survival (All EHSS No Population) Per BICR in Participants With LAG-3 Positive Status(≥1% by IHC)
Progression free survival (PFS) is defined as time from on treatment to disease progression or death (whichever comes first). Disease progression is defined as unequivocal progression of existing non-target lesions.
Measured: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 3 years)
Objective Response Rate (ORR) Per BICR - All Comer Population in Participants With LAG-3 Positive Status(≥1% by IHC)
Objective response rate (ORR) is defined as the percentage of participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on blinded independent central review (BICR) assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 3 years)
Objective Response Rate (ORR) Per BICR - All EHSS No Population in Participants With LAG-3 Positive Status(≥1% by IHC)
Objective response rate (ORR) is defined as the percentage of participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on blinded independent central review (BICR) assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 3 years)
Number of Participants With Adverse Events
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) 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.
Measured: From first dose (Day 1) to 30 days after last dose (up to approximately 36 months)
Number of Participants With Select Adverse Events
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Measured: From first dose (Day 1) to 30 days after last dose (up to approximately 36 months)
Number of Participants With Immune Mediated Endocrine Adverse Events
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Measured: From first dose (Day 1) to 30 days after last dose (up to approximately 36 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2022
- Study start5 May 2022
- Primary completion5 Jul 2025
- Study completion18 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05337137
- Sponsor's protocol ID
- CA224-106
- Other IDs
- 2021-003606-53, U1111-1267-1579
- Acronym
- RELATIVITY-106
- Status last verified
- Sep 2026
- First submitted
- 13 Apr 2022
- Last updated
- 14 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available