LIVIGNO-2: 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)

Sponsor

AbbVie (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06109272

Collaborator

(none)

660

Enrollment

Arms

77.4

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Hepatocellular carcinoma (HCC) is a common cancer worldwide and a leading cause of cancer-related death. The majority of participants first presenting with HCC have advanced unresectable or metastatic disease. The purpose of this study is to evaluate the optimized dose, adverse events, and efficacy of livmoniplimab in combination with budigalimab.

Livmoniplimab is an investigational drug being developed for the treatment of HCC. There are 2 stages to this study. In Stage 1, there are 3 treatment arms and participants will be randomized in a 1:1:1 ratio. Participants will either receive livmoniplimab (at different doses) in combination with budigalimab (another investigational drug), atezolizumab in combination with bevacizumab, or tremelimumab in combination with durvalumab. In Stage 2, there are 2 treatments arms and participants will be randomized in a 1:1 ratio. Participants will either receive livmoniplimab (optimized dose) in combination with budigalimab or tremelimumab in combination with durvalumab. Approximately 660 adult participants will be enrolled in the study across 185 sites worldwide.

Stage 1: In arm 1, participants will receive intravenously (IV) infused livmoniplimab (Dose

in combination with IV infused budigalimab, every 3 weeks. In arm 2, participants will receive IV infused livmoniplimab (Dose 2) in combination with IV infused budigalimab, every 3 weeks. In Arm 3 (control), participants will receive the investigator's choice: IV atezolizumab in combination with IV bevacizumab every 3 weeks or single dose IV tremelimumab in combination with IV durvalumab every 4 weeks. Stage 2: In arm 1, participants will receive IV infused livmoniplimab (optimized dose) in combination with IV infused budigalimab, every 3 weeks. In Arm 2 (control), participants will receive single dose IV tremelimumab in combination with IV durvalumab every 4 weeks. All participants will continue treatment until disease progression or discontinuation criteria are met, whichever occurs first. The estimated duration of this study is about 56 months.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, questionnaires, and scans.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Livmoniplimab Drug: Budigalimab Drug: Durvalumab Drug: Atezolizumab Drug: Bevacizumab Drug: Tremelimumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

660 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2/3, Randomized Study to Evaluate the Dose Optimization, Safety, and Efficacy of Livmoniplimab in Combination With Budigalimab in Subjects With Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) Who Have Not Previously Received Systemic Treatment

Anticipated Study Start Date :

Jan 16, 2024

Anticipated Primary Completion Date :

Jun 29, 2030

Anticipated Study Completion Date :

Jun 29, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stage 1: Cohort 1 Participants will receive livmoniplimab Dose 1 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.	Drug: Livmoniplimab Intravenous (IV) Solution Other Names: ABBV-151 Drug: Budigalimab Intravenous (IV) Solution Other Names: ABBV-181
Experimental: Stage 1: Cohort 2 Participants will receive livmoniplimab Dose 2 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.	Drug: Livmoniplimab Intravenous (IV) Solution Other Names: ABBV-151 Drug: Budigalimab Intravenous (IV) Solution Other Names: ABBV-181
Active Comparator: Stage 1: Cohort 3 - Group 1 (Control) Participants will receive atezolizumab in combination with bevacizumab every 3 weeks until disease progression or until discontinuation criteria are met.	Drug: Atezolizumab Intravenous (IV) Solution Drug: Bevacizumab Intravenous (IV) Solution
Active Comparator: Stage 1: Cohort 3 - Group 2 (Control) Participants will receive a single dose of tremelimumab in combination with durvalumab every four weeks until disease progression or until discontinuation criteria are met.	Drug: Durvalumab Intravenous (IV) Solution Drug: Tremelimumab Intravenous (IV) Solution
Experimental: Stage 2: Arm 1 Participants will receive livmoniplimab (optimized dose) in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.	Drug: Livmoniplimab Intravenous (IV) Solution Other Names: ABBV-151 Drug: Budigalimab Intravenous (IV) Solution Other Names: ABBV-181
Active Comparator: Stage 2: Arm 2 (Control) Participants will receive a single dose of tremelimumab in combination with durvalumab every 4 weeks until disease progression or until discontinuation criteria are met.	Drug: Durvalumab Intravenous (IV) Solution Drug: Tremelimumab Intravenous (IV) Solution

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.