Unresectable Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular carcinoma; HCC; nivolumab; ipilimumab
Brief summary
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.
Interventions
COMBINATION_PRODUCTNivolumab plus ipilimumab
According to product label
Sponsors
Bristol-Myers Squibb
Ono Pharmaceutical Co., Ltd.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of nivolumab plus ipilimumab treatment cycles per participant | Up to 2 years | Total number of administered cycles of nivolumab plus ipilimumab given every 3 weeks, summarized per participant. |
| Number of participants who discontinue treatment | Up to 2 years | Number of participants who discontinue nivolumab plus ipilimumab. |
| Reasons for treatment discontinuation | Up to 2 years | Distribution of reasons, including disease progression, adverse events death, participant request, transfer, or other reasons as assessed by treating clinician. |
| Number of participants with grade ≥3 immune-mediated liver injury (IMLI) | Up to 2 years | 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. |
| Time to onset of immune-mediated liver injury (IMLI) | Up to 2 years | Time from first dose of nivolumab plus ipilimumab to first occurrence of immune-mediated liver injury (any grade). |
| Time to resolution of immune-mediated liver injury (IMLI) | Up to 2 years | Time from onset of immune-mediated liver injury to resolution, defined as recovery, recovery with sequelae, or improvement per clinician assessment. |
| 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) | Up to 2 years | 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. |
| Best overall response (BOR) | Up to 2 years | 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. |
| Disease control rate (DCR | Up to 2 years | 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. |
| Duration of nivolumab plus ipilimumab combination therapy | Up to 2 years | Time from first dose of nivolumab plus ipilimumab to treatment discontinuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to onset of immune-mediated adverse events (IMAEs) | Up to 2 years | Time from treatment initiation to onset of immune-mediated adverse events. |
| Time to resolution of immune-mediated adverse events (IMAEs) | Up to 2 years | Time from onset of immune-mediated adverse events to resolution. |
| 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) | Up to 2 years | Number of participants experiencing treatment-related adverse events categorized by preferred term and CTCAE v5.0 grade. |
| Time to onset of treatment-related adverse events (TRAEs) | Up to 2 years | Time from treatment initiation to onset of immune-mediated adverse events. |
| Duration of response (DOR) | Up to 2 years | 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 |
| Time to resolution of treatment-related adverse events (TRAEs) | Up to 2 years | Time from onset of immune-mediated adverse events to resolution. |
| Overall survival (OS | Up to 2 years | Time from first dose of nivolumab plus ipilimumab to death from any cause. |
| Progression-free survival (PFS) | Up to 2 years | 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. |
| Second progression-free survival (PFS2) | Up to 2 years | Time from first dose of nivolumab plus ipilimumab to progression after second-line therapy or death from any cause, whichever occurs first. |
| Depth of response (DpR) | Up to 2 years | Maximum percentage reduction from baseline in the sum of diameters of target lesions among participants with measurable disease. |
| Change from baseline in Child-Pugh score | Up to 2 years | Change from baseline in Child-Pugh score (range 5-15), including classification into Class A, B, or C. |
| 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 | Up to 2 years | Number of participants who receive any subsequent anticancer therapy after discontinuation of nivolumab plus ipilimumab |
| Type of subsequent therapy received | Up to 2 years | 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. |
| Number of participants with treatment-related adverse events (TRAEs) leading to treatment discontinuation | 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 immune-mediated adverse events (IMAEs) | Up to 2 years | Number of participants experiencing IMAEs, defined as treatment-related adverse events with immune-mediated etiology, categorized by CTCAE v5.0 grade (1-5). |
Countries
Japan
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed