First-Line Nivolumab Plus Ipilimumab in Unresectable Hepatocellular Carcinoma (J-PROMISE)

Prospective Observational Study of First-Line Nivolumab Plus Ipilimumab in Patients With Unresectable Hepatocellular Carcinoma in Japan (J-PROMISE)

This study looks at how a combination of two medicines, nivolumab and ipilimumab, is used to treat people with advanced liver cancer that cannot be removed by surgery. The study will follow adults receiving this treatment in routine medical care in Japan to understand how safe it is, how well it works, and how it is used in standard clinical practice.

Study Overview

• Status: Recruiting
• Conditions: Unresectable Hepatocellular Carcinoma
• Intervention / Treatment: Combination product: Nivolumab plus ipilimumab

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: First line of the email MUST contain NCT # and Site #.
• Study Contact Backup: Name: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com

Study Locations

• Japan
  • Chiba, Japan
    • Recruiting
    • National Cancer Center Hospital East
  • Tokyo
    • Minato-ku, Tokyo, Japan, 1050001
      • Recruiting
      • Mebix. Inc
      • Contact: Minoru Tonogai, Site 0001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults in Japan with Child-Pugh class A unresectable hepatocellular carcinoma initiating first-line nivolumab plus ipilimumab in routine clinical practice.

Description

Inclusion Criteria:

• Participants aged ≥ 18 years at the time of consent
• Participants with unresectable hepatocellular carcinoma (uHCC), defined as disease not eligible for curative surgical and/or locoregional therapies, or progressive disease after surgical and/or locoregional therapies
• Child-Pugh class A (total score 5-6)

• Participants who have not received prior systemic drug therapy for uHCC

  • Participants who relapsed more than 6 months after completion of postoperative adjuvant therapy are eligible
  • Participants who received lenvatinib in combination with transarterial chemoembolization (TACE) are eligible if the treating physician determined they were eligible for TACE; participants are excluded if TACE eligibility at the time of lenvatinib initiation is unclear

• Participants scheduled to initiate nivolumab plus ipilimumab combination therapy between March 1, 2026 and February 28, 2027

  • Nivolumab plus ipilimumab combination therapy is defined as nivolumab 80 mg and ipilimumab 3 mg/kg administered intravenously every 3 weeks for 4 cycles, followed by nivolumab monotherapy at 240 mg every 2 weeks or 480 mg every 4 weeks
• Participants who provide written informed consent prior to initiation of nivolumab plus ipilimumab therapy

Exclusion Criteria:

• Known fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, or mixed cholangiocarcinoma
• Prior liver transplant
• ECOG performance status ≥ 3
• Uncontrolled comorbidities despite treatment
• Other advanced cancers requiring systemic therapy
• Prior immuno-oncology treatment
• Participation in interventional clinical trials at enrollment
• Deemed unsuitable by investigator

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Nivolumab plus ipilimumab cohort; Participants with unresectable hepatocellular carcinoma receiving nivolumab plus ipilimumab as first-line systemic therapy in routine clinical practice in Japan.	Combination product: Nivolumab plus ipilimumab; According to product label

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with grade ≥3 immune-mediated liver injury (IMLI)	Number of participants who experience grade 3-5 immune-mediated liver injury (IMLI), defined as treatment-related hepatic adverse events assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	Up to 2 years
Time to onset of immune-mediated liver injury (IMLI)	Time from first dose of nivolumab plus ipilimumab to first occurrence of immune-mediated liver injury (any grade).	Up to 2 years
Time to resolution of immune-mediated liver injury (IMLI)	Time from onset of immune-mediated liver injury to resolution, defined as recovery, recovery with sequelae, or improvement per clinician assessment.	Up to 2 years
Number of participants with immune-mediated liver injury (IMLI) who achieve resolution (recovered, recovering, or recovered with sequelae)		Up to 2 years
Treatment prescribed to participants for immune-mediated liver injury (IMLI)		Up to 2 years
Objective response rate (ORR)	Number of participants with complete response (CR) or partial response (PR) as best overall response among participants with baseline target lesions, assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Up to 2 years
Best overall response (BOR)	Distribution of best overall response categorized as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE) among participants with baseline target lesions per RECIST v1.1.	Up to 2 years
Disease control rate (DCR	Number of participants with complete response (CR), partial response (PR), or stable disease (SD) as best overall response among participants with baseline target lesions per RECIST v1.1.	Up to 2 years
Duration of nivolumab plus ipilimumab combination therapy	Time from first dose of nivolumab plus ipilimumab to treatment discontinuation.	Up to 2 years
Number of nivolumab plus ipilimumab treatment cycles per participant	Total number of administered cycles of nivolumab plus ipilimumab given every 3 weeks, summarized per participant.	Up to 2 years
Number of participants who discontinue treatment	Number of participants who discontinue nivolumab plus ipilimumab.	Up to 2 years
Reasons for treatment discontinuation	Distribution of reasons, including disease progression, adverse events death, participant request, transfer, or other reasons as assessed by treating clinician.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with immune-mediated adverse events (IMAEs)	Number of participants experiencing IMAEs, defined as treatment-related adverse events with immune-mediated etiology, categorized by CTCAE v5.0 grade (1-5).	Up to 2 years
Time to onset of immune-mediated adverse events (IMAEs)	Time from treatment initiation to onset of immune-mediated adverse events.	Up to 2 years
Time to resolution of immune-mediated adverse events (IMAEs)	Time from onset of immune-mediated adverse events to resolution.	Up to 2 years
Number of participants with immune-mediated adverse events (IMAEs) who achieve resolution (recovered, recovering, or recovered with sequelae)		Up to 2 years
Treatment prescribed to participants for immune-mediated adverse events (IMAEs)		Up to 2 years
Number of participants with of immune-mediated adverse events (IMAEs) leading to treatment discontinuation		Up to 2 years
Number of participants with treatment-related adverse events (TRAEs)	Number of participants experiencing treatment-related adverse events categorized by preferred term and CTCAE v5.0 grade.	Up to 2 years
Time to onset of treatment-related adverse events (TRAEs)	Time from treatment initiation to onset of immune-mediated adverse events.	Up to 2 years
Time to resolution of treatment-related adverse events (TRAEs)	Time from onset of immune-mediated adverse events to resolution.	Up to 2 years
Number of participants with treatment-related adverse events (TRAEs) who achieve resolution (recovered, recovering, or recovered with sequelae)		Up to 2 years
Number of participants with treatment-related adverse events (TRAEs) leading to treatment discontinuation		Up to 2 years
Duration of response (DOR)	Time from first documented complete response (CR) or partial response (PR) to disease progression per RECIST v1.1 or death from any cause, whichever occurs first	Up to 2 years
Overall survival (OS	Time from first dose of nivolumab plus ipilimumab to death from any cause.	Up to 2 years
Progression-free survival (PFS)	Time from first dose of nivolumab plus ipilimumab to first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first.	Up to 2 years
Second progression-free survival (PFS2)	Time from first dose of nivolumab plus ipilimumab to progression after second-line therapy or death from any cause, whichever occurs first.	Up to 2 years
Depth of response (DpR)	Maximum percentage reduction from baseline in the sum of diameters of target lesions among participants with measurable disease.	Up to 2 years
Change from baseline in Child-Pugh score	Change from baseline in Child-Pugh score (range 5-15), including classification into Class A, B, or C.	Up to 2 years
Change from baseline in albumin-bilirubin (ALBI) and modified ALBI (mALBI) grades based on laboratory values.		Up to 2 years
Number of participants receiving subsequent therapy	Number of participants who receive any subsequent anticancer therapy after discontinuation of nivolumab plus ipilimumab	Up to 2 years
Type of subsequent therapy received	Distribution of subsequent therapies received after discontinuation of nivolumab plus ipilimumab, including transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), radiofrequency ablation (RFA), surgery, radiation therapy, and systemic therapies.	Up to 2 years

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co., Ltd.
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2026
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): February 29, 2028

Study Registration Dates

• First Submitted: June 25, 2026
• First Submitted That Met QC Criteria: June 25, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Hepatocellular carcinoma; HCC; nivolumab; ipilimumab
• 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; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; Ipilimumab
• Other Study ID Numbers: CA209-1554

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No