Hepatocellular CarcinomaPhase 1NCT04658147
Nivolumab With or Without Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma
A Phase 1 study testing Nivolumab and Relatlimab in people with Hepatocellular Carcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.
Trial summary
The purpose of this study is to determine the safety and feasibility of neoadjuvant/adjuvant Nivolumab or Nivolumab plus Relatlimab in patients with HCC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Nivolumab and Relatlimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- 28 May 2021to 1 Jun 2030
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Technically resectable HCC as defined by:
- HCC may be diagnosed pathologically, or noninvasively by the American Association for the Study of Liver Diseases (AASLD) criteria or the Organ Procurement and Transplant Network (OPTN) Obligatory Diagnostic Criteria for Hepatocellular Carcinoma (HCC).
- No extrahepatic spread, no nodal disease, and no bilateral left and right branch portal vein involvement.
- Measurable disease per RECIST 1.1 as determined by the investigator.
- Age ≥ 18 years old on the day of consent.
- ECOG performance status ≤1 or Karnofsky ≥80.
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- Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.
- Patients must have adequate liver remnant and function.
- Antiviral therapy per local standard of care for hepatitis B.
- LVEF assessment with documented LVEF ≥ 50% by either TTE or MUGA (TTE preferred) within 6 months from first study drug administration.
- Woman of child-bearing potential must have a negative pregnancy test.
- Must use acceptable form of birth control while on study.
- Ability to understand and willingness to sign a written informed consent document.
Who cannot join
- Fibrolamellar carcinoma or mixed HCC.
- Receiving, or previously received, any systemic chemotherapy, or investigational agent for HCC.
- Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, or anti-Lag-3 antibodies.
- Has a known additional malignancy that is expected to require active treatment within two years, or is likely to be life-limiting in the opinion of the treating investigator. Superficial bladder cancer, non-melanoma skin cancers, or low grade prostate cancer not requiring therapy would not exclude participation in this trial.
- History of HIV infection.
- Active co-infection with HBV and HDV.
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- Has a diagnosis of immunodeficiency, or is receiving systemic steroid therapy.
- Prior tissue or organ allograft or allogeneic bone marrow transplantation.
- History of any autoimmune disease requiring systemic treatment within the past 2 years.
- Systemic or topical corticosteroids at immunosuppressive doses (> 10 mg/day of prednisone or equivalent).
- Confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
- Uncontrolled intercurrent illness.•
- Uncontrolled or significant cardiovascular disease.
- Significant heart disease.
- Moderate or severe ascites.
- Known or suspected hypersensitivity to study treatment.
- Are pregnant or breastfeeding.
- WOCBP and men with female partners (WOCBP) who are not willing to use contraception.
- Unable to have blood drawn.
- Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
- Any illicit drugs or other substance abuse.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
The Ohio State University, Wexner Medical Center
Columbus, Ohio, 43210-1002
About this study
Official title: Feasibility and Efficacy of Perioperative Nivolumab With or Without Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC)
The purpose of this study is to determine the safety and feasibility of neoadjuvant/adjuvant Nivolumab or Nivolumab plus Relatlimab in patients with HCC.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Nivolumab, Relatlimab
- Keywords
- Relatlimab, Nivolumab, Immunotherapy, Anti PD-1, Anti - LAG-3, Resectable hepatocellular Cancer, Potentially resectable hepatocellular Cancer, Hepatocellular Cancer (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.
NivolumabDrug
Also called OPDIVO™, BMS 936558, MDX1106, ONO-4538
Patients received 480mg Nivolumab as a 30 minute IV infusion on Day 1 of Cycles 1 and 2 (28 day cycles) prior to surgery. Post-surgery, patients received an additional 10 doses of adjuvant 480mg Nivolumab therapy on Day 1 of each cycle (every 28 days).
RelatlimabDrug
Also called BMS-986016, BMS-986016-01, Anti-LAG-3
Patients received either 480mg or 960mg Relatlimab as a 30 minute IV infusion on Day 1 of Cycles 1 and 2 (28 day cycles) prior to surgery. Post-surgery, patients received an additional 10 doses of adjuvant 480mg or 960mg Relatlimab therapy on Day 1 every 28 days. Dosing was changed from 960mg to 480mg based on guidance from Bristol Myers Squibb.
| Study group | Role | What they receive |
|---|---|---|
| Arm A - Nivolumab | Experimental | Participants receive Nivolumab only. Receives: Drug: Nivolumab |
| Arm B - Nivolumab and Relatlimab | Experimental | Participants receive Nivolumab and Relatlimab. Receives: Drug: Nivolumab; Drug: Relatlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Precluded From Surgery
Number of patients that experienced a treatment-related adverse event that precludes continuing on to surgery within 60 days of the last dose of neoadjuvant treatment. Individuals who do not go on to receive surgery due to other causes (e.g. progressive disease, patient refusal) will not be counted as feasibility failures.
Measured: Up to 2 months
Secondary outcomes (14)
Number of Participants Experiencing Grade 3 or Above Study Drug-related Adverse Event (AE)
When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject.
Measured: Up to 15 months
Number of Participants Who Obtain R0 Resection
Number of evaluable participants who obtain R0 resection. R0 resection rate will be estimated among the patients who receive at least one dose of neoadjuvant treatment and went to surgery. R0 resection is defined by a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed.
Measured: Up to 2 months
Number of Evaluable Patients With Pathologic Response to Treatment
Pathologic response includes pathologic complete response (pCR) or major pathologic responses (MPR). Pathologic response will be evaluated in patients who receive at least one dose of study drug and receive surgery.
Measured: Up to 2 months
Objective Response Rate (ORR) at 8 Weeks Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1).
Objective response rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1at 8 weeks. CR = Disappearance af all target lesions, PR = >30% decrease in the sum of diameters of target lesions. Participants who discontinue due to toxicity or clinical progression prior to post-baseline tumor assesment will be considered as non-responders. Participants who discontinue for other reasons prior to their first dose of study drug will not be included in the analysis.
Measured: 8 weeks
Overall Survival (OS) Rate at 12 Months
OS rate is defined as the proportion of patients who are alive at 12 months. Estimation based on the Kaplan-Meier curve.
Measured: 12 months
Overall Survival (OS) Rate at 18 Months
OS rate is defined as the proportion of patients who are alive at 18 months. Estimation based on the Kaplan-Meier curve.
Measured: 18 months
Overall Survival (OS) at 3 Years
OS rate is defined as the proportion of patients who are alive at 3 years. Estimation based on the Kaplan-Meier curve.
Measured: 3 years
Overall Survival (OS) at 5 Years
OS rate is defined as the proportion of patients who are alive at 12 months. Estimation based on the Kaplan-Meier curve.
Measured: 5 years
Disease Free Survival (DFS) Rate at 12 Months
The 12 months DFS rate is defined as the Kaplan-Meier estimate of the proportion of patients alive and free of disease recurrence at 12 months from date of definitive freedom of disease. Patients who did not experience disease-free status were excluded from this calculation.
Measured: 12 months
Disease Free Survival (DFS) at 18 Months
The 18 months DFS rate is defined as the Kaplan-Meier estimate of the proportion of patients alive and free of disease recurrence at 18 months from date of definitive freedom of disease. Patients who did not experience disease-free status were excluded from this calculation.
Measured: 18 months
Disease Free Survival (DFS) at 3 Years
The 3 years DFS rate is defined as the Kaplan-Meier estimate of the proportion of patients alive and free of disease recurrence at 3 years from date of definitive freedom of disease. Patients who did not experience disease-free status were excluded from this calculation.
Measured: 3 years
Disease Free Survival (DFS) at 5 Years
The 5 years DFS rate is defined as the Kaplan-Meier estimate of the proportion of patients alive and free of disease recurrence at 5 years from date of definitive freedom of disease. Patients who did not experience disease-free status were excluded from this calculation.
Measured: 5 years
Overall Survival (OS)
Median OS will be measured from date of randomization or eligibility confirmation until death or end of follow-up. OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis. Estimation based on the Kaplan-Meier curve.
Measured: 6 years
Disease Free Survival (DFS)
Median DFS is defined as the duration of time from date of randomization or eligibility confirmation to the date of disease progression precluding surgery, disease progression or recurrence at or after surgery, or death, whichever occurs first. Patients will be censored at date of last scan, unless they developed a second, unrelated primary tumor, in which they will be censored at the last scan prior to cancer-directed therapy for the second tumor. Estimation based on the Kaplan-Meier curve.
Measured: Up to 57 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2020
- Study start28 May 2021
- Primary completion2 Sep 2025
- Study completion1 Jun 2030 (estimated)
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 Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Mark Yarchoan, MD, Principal investigator, SKCCC Johns Hopkins Medical Institution
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04658147
- Sponsor's protocol ID
- J20121
- Other IDs
- IRB00246739
- Status last verified
- Oct 2026
- First submitted
- 1 Dec 2020
- Last updated
- 28 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility and Efficacy of Perioperative Nivolumab With or Without Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT04658147
- Acronym / sponsor ID
- J20121
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Relatlimab, Nivolumab, Immunotherapy, Anti PD-1, Anti - LAG-3, Resectable hepatocellular Cancer, Potentially resectable hepatocellular Cancer, Hepatocellular Cancer (HCC)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 28 May 2021 (actual)
- Primary completion
- 2 Sep 2025 (actual)
- Study completion
- 1 Jun 2030 (estimated)
- First posted
- 8 Dec 2020 (actual)
- Results
- Posted 28 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety and feasibility of neoadjuvant/adjuvant Nivolumab or Nivolumab plus Relatlimab in patients with HCC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A - Nivolumab | Experimental | Drug: NivolumabParticipants receive Nivolumab only. |
| Arm B - Nivolumab and Relatlimab | Experimental | Drug: Nivolumab, Drug: RelatlimabParticipants receive Nivolumab and Relatlimab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Technically resectable HCC as defined by:
- Measurable disease per RECIST 1.1 as determined by the investigator.
- Age ≥ 18 years old on the day of consent.
- ECOG performance status ≤1 or Karnofsky ≥80.
- Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.
Key exclusion criteria (21 listed)
- Fibrolamellar carcinoma or mixed HCC.
- Receiving, or previously received, any systemic chemotherapy, or investigational agent for HCC.
- Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, or anti-Lag-3 antibodies.
- Has a known additional malignancy that is expected to require active treatment within two years, or is likely to be life-limiting in the opinion of the treating investigator. Superficial bladder cancer, non-melanoma skin cancers, or low grade prostate cancer not requiring therapy would not exclude participation in this trial.
- History of HIV infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OPDIVO™, BMS 936558, MDX1106, ONO-4538Patients received 480mg Nivolumab as a 30 minute IV infusion on Day 1 of Cycles 1 and 2 (28 day cycles) prior to surgery. Post-surgery, patients received an additional 10 doses of adjuvant 480mg Nivolumab therapy on Day 1 of each cycle (every 28 days). | Drug | Arm A - Nivolumab, Arm B - Nivolumab and Relatlimab |
| RelatlimabAlso: BMS-986016, BMS-986016-01, Anti-LAG-3Patients received either 480mg or 960mg Relatlimab as a 30 minute IV infusion on Day 1 of Cycles 1 and 2 (28 day cycles) prior to surgery. Post-surgery, patients received an additional 10 doses of adjuvant 480mg or 960mg Relatlimab therapy on Day 1 every 28 days. Dosing was changed from 960mg to 480mg based on guidance from Bristol Myers Squibb. | Drug | Arm B - Nivolumab and Relatlimab |
Primary outcome
Number of Patients Precluded From Surgery
Time frame: Up to 2 months
Number of patients that experienced a treatment-related adverse event that precludes continuing on to surgery within 60 days of the last dose of neoadjuvant treatment. Individuals who do not go on to receive surgery due to other causes (e.g. progressive disease, patient refusal) will not be counted as feasibility failures.
14 secondary outcomes
Number of Participants Experiencing Grade 3 or Above Study Drug-related Adverse Event (AE)
Time frame: Up to 15 months
Number of Participants Who Obtain R0 Resection
Time frame: Up to 2 months
Number of Evaluable Patients With Pathologic Response to Treatment
Time frame: Up to 2 months
Objective Response Rate (ORR) at 8 Weeks Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1).
Time frame: 8 weeks
Overall Survival (OS) Rate at 12 Months
Time frame: 12 months
Overall Survival (OS) Rate at 18 Months
Time frame: 18 months
Overall Survival (OS) at 3 Years
Time frame: 3 years
Overall Survival (OS) at 5 Years
Time frame: 5 years
Disease Free Survival (DFS) Rate at 12 Months
Time frame: 12 months
Disease Free Survival (DFS) at 18 Months
Time frame: 18 months
Disease Free Survival (DFS) at 3 Years
Time frame: 3 years
Disease Free Survival (DFS) at 5 Years
Time frame: 5 years
Overall Survival (OS)
Time frame: 6 years
Disease Free Survival (DFS)
Time frame: Up to 57 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Yarchoan, MD principal investigator
SKCCC Johns Hopkins Medical Institution
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab and Relatlimab in people with Hepatocellular Carcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Precluded From Surgery (time frame: Up to 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.