A Study to Assess the Dose, Adverse Events, and Change in Disease Activity of Livmoniplimab as an Intravenous (IV) Solution in Combination With Budigalimab as an IV Solution in Adult Participants With Hepatocellular Carcinoma (HCC)

• Livmoniplimab (Drug), also known as ABBV-151: Intravenous (IV) Solution
• Budigalimab (Drug), also known as ABBV-181: Intravenous (IV) Solution
• Durvalumab (Drug): Intravenous (IV) Solution
• Atezolizumab (Drug): Intravenous (IV) Solution
• Bevacizumab (Drug): Intravenous (IV) Solution
• Tremelimumab (Drug): Intravenous (IV) Solution

Primary outcomes

• Stage 1: Best Overall Response (BOR) per Investigator [Through Study Completion, Up to Approximately 56 Months]: BOR is defined as a participant achieving confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by investigators at any time prior to subsequent anticancer therapy.
• Stage 2: Overall Survival (OS) [Through Study Completion, Up to Approximately 56 Months]: OS is defined as the time from randomization until death from any cause

Secondary outcomes

• Stage 1: Number of Participants with Progression-Free Survival (PFS) [Through Study Completion, Up to Approximately 56 Months]: PFS is defined as the time from randomization until the first documentation of progressive disease according to RECIST 1.1 as determined by investigators or death from any cause, whichever occurs first.
• Stage 1: Duration of Response (DOR) per Investigator [Through Study Completion, Up to Approximately 56 Months]: DOR is defined as the time from first confirmed CR or PR until the first documentation of progressive disease according to RECIST 1.1 as determined by investigators or death from any cause, whichever occurs first.
• Stage 1: Overall Survival (OS) [Through Study Completion, Up to Approximately 56 Months]: OS is defined as the time from randomization until death from any cause.
• Stage 1: Number of Participants with Adverse Events (AEs) [Through Study Completion, Up to Approximately 56 Months]: An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
• Stage 1: Maximum Plasma Concentration (Cmax) of Livmoniplimab and Budigalimab [Through Study Completion, Up to Approximately 56 Months]: Cmax of livmoniplimab and budigalimab.
• Stage 1: Time to Cmax (Tmax) of Livmoniplimab and Budigalimab [Through Study Completion, Up to Approximately 56 Months]: Tmax of livmoniplimab and budigalimab.
• Stage 1: Area Under the Serum Concentration Versus Time Curve (AUC) of Livmoniplimab and Budigalimab [Through Study Completion, Up to Approximately 56 Months]: AUC of livmoniplimab and budigalimab.
• Stage 2: Number of Participants with Progression-Free Survival (PFS) [Through Study Completion, Up to Approximately 56 Months]: PFS is defined as the time from randomization until the first documentation of progressive disease according to RECIST 1.1 as determined blinded independent central review (BICR) or death from any cause, whichever occurs first.
• Stage 2: Best Overall Response (BOR) of Complete Response (CR)/Partial Response (PR) per BICR [Through Study Completion, Up to Approximately 56 Months]: BOR is defined as a participant achieving confirmed CR/PR per RECIST 1.1 as determined by BICR at any time prior to subsequent anticancer therapy.
• Change from Baseline in the Pain Domain of the European Organization for Research Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-Question Module (EORTC QLQ-HCC18) [Baseline to Week 12]: The EORTC QLQ-HCC18 is an 18-item scale that measures hepatocellular carcinoma (HCC)-specific symptoms and health-related quality of life (HRQoL). The Pain Domain contains 2 items where scores are based on a 4-point Likert scale (with 1 = 'not at all' to 4 = 'very much'); scaled scores for each domain ranged from 0-100 with a higher score indicating worse symptoms.
• Change from Baseline in the Fatigue Domain of the EORTC QLQ-HCC18 [Baseline to Week 12]: The EORTC QLQ-HCC18 is an 18-item scale that measures HCC-specific symptoms and HRQoL. The Fatigue Domain contains 3 items where scores are based on a 4-point Likert scale (with 1 = 'not at all' to 4 = 'very much'); scaled scores for each domain ranged from 0-100 with a higher score indicating worse symptoms.
• Change from Baseline in Physical Function (PF) Domain of the European Organization for Research Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) [Baseline to Week 12]: The EORTC QLQ-C30 is an 30-item patient-reported questionnaire that measures symptoms and HRQoL. The PF Domain is a functional scale where participants rate items on a 4-point scale (with 1 = 'not at all' to 4 = 'very much'). A change of 5 to 10 points is considered a small change and the lower bound (5) will be used to define the minimum important difference. A change of >= 10 to < 20 points is considered a moderate change.
• Change from Baseline in Global Health Status (GHS)/Quality of Life (QoL) Domain as Measured by the GHS/QoL Domain of the EORTC QLQ-C30 [Baseline to Week 12]: The EORTC QLQ-C30 is an 30-item patient-reported questionnaire that measures symptoms and HRQoL. The GHS/QoL Domain is a scale where participants rate items on a 4-point scale (with 1 = 'not at all' to 4 = 'very much'). A change of 5 to 10 points is considered a small change and the lower bound (5) will be used to define the minimum important difference. A change of ≥ 10 to < 20 points is considered a moderate change.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology or cytology or clinically by American Association for the Study of Liver Diseases criteria for participants with cirrhosis.
* Barcelona Clinic Liver Cancer (BCLC) Stage B or C.
* Child-Pugh A or B7 classification (i.e., total Child-Pugh score of 5, 6, or 7).
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.

Exclusion Criteria:

* Prior systemic therapy for HCC.
* Symptomatic, untreated, or actively progressing CNS metastases.
* History of malignancy other than HCC.

• ABBVIE INC., Study director, AbbVie

NIH grants: 2023