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) (LIVIGNO-2)

AbbVie

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Hepatocellular Carcinoma

Treatments: Drug: Budigalimab; Drug: Durvalumab; Drug: Atezolizumab; Drug: Tremelimumab; Drug: Bevacizumab; Drug: Livmoniplimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06109272

2023-504600-28-00 (Other Identifier)

M24-052

Details and patient eligibility

About

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 1) 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.

Enrollment: 660 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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660 participants in 6 patient groups

Stage 1: Cohort 1

Experimental group

Description:

Participants will receive livmoniplimab Dose 1 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.

Treatment:

Drug: Livmoniplimab

Drug: Budigalimab

Stage 1: Cohort 2

Experimental group

Description:

Participants will receive livmoniplimab Dose 2 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.

Treatment:

Drug: Livmoniplimab

Drug: Budigalimab

Stage 1: Cohort 3 - Group 1 (Control)

Active Comparator group

Description:

Participants will receive atezolizumab in combination with bevacizumab every 3 weeks until disease progression or until discontinuation criteria are met.

Treatment:

Drug: Bevacizumab

Drug: Atezolizumab

Stage 1: Cohort 3 - Group 2 (Control)

Active Comparator group

Description:

Participants will receive a single dose of tremelimumab in combination with durvalumab every four weeks until disease progression or until discontinuation criteria are met.

Treatment:

Drug: Tremelimumab

Drug: Durvalumab

Stage 2: Arm 1

Experimental group

Description:

Participants will receive livmoniplimab (optimized dose) in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met.

Treatment:

Drug: Livmoniplimab

Drug: Budigalimab

Stage 2: Arm 2 (Control)

Active Comparator group

Description:

Participants will receive a single dose of tremelimumab in combination with durvalumab every 4 weeks until disease progression or until discontinuation criteria are met.

Treatment:

Drug: Tremelimumab

Drug: Durvalumab