Study to Evaluate Adverse Events, and Change in Disease Activity, When Intravenously (IV) Infused With Livmoniplimab in Combination With IV Infused Budigalimab in Adult Participants With Hepatocellular Carcinoma (HCC)

Study Overview
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Brief Summary
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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 3 treatment arms in this study 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), lenvatinib, or sorafenib. Approximately 120 adult participants will be enrolled in the study across 60 sites worldwide. In arm 1 (control), participants will receive the investigator's choice: lenvatinib as an oral capsule or sorafenib as an oral tablet, once daily. In arm 2, participants will receive intravenously (IV) infused livmoniplimab (dose A) in combination with IV infused budigalimab, every 3 weeks. In arm 3, participants will receive intravenously (IV) infused livmoniplimab (dose B) in combination with IV infused budigalimab, every 3 weeks. The estimated duration of the study is up to 2 years 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.

Official Title
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A Phase 2, Randomized Study to Evaluate the Optimized Dose, Safety, and Efficacy of Livmoniplimab in Combination With Budigalimab for Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) Patients Who Have Progressed After an Immune Checkpoint Inhibitor Containing Regimen in First-Line HCC

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Budigalimab
* Drug: Livmoniplimab
* Drug: Lenvatinib
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Child-Pugh A classification. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. Received an immune checkpoint inhibitor in first-line (1L) hepatocellular carcinoma (HCC) treatment regimen. Adequate hematologic and end-organ function. Tissue biopsy at screening. Disease that is not amenable to surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies. Exclusion Criteria: Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. Prior treatment with an approved tyrosine kinase inhibitor (for example sorafenib or Lenvatinib) in 1L HCC treatment regimen. History of malignancy other than hepatocellular carcinoma (HCC) within 5 years prior to screening. Hepatic encephalopathy or requirement for medications to prevent or control encephalopathy. Moderate or severe ascites requiring recurrent non-pharmacologic intervention to maintain symptomatic control. Coinfection with active HBV infection and active HCV infection. Prior history of grade 3 or higher immune-mediated adverse event or discontinuation due to immune-mediated adverse events. Prior history of recurrent grade 2 or higher interstitial lung disease/pneumonitis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1: Lenvatinib or Sorafenib<br>Participants will receive Lenvatinib or or Sorafenib, as part of an approximately 2 year treatment period. | Drug: Lenvatinib<br>* Oral: Capsule<br>Drug: Sorafenib<br>* Oral: Tablet<br>|
| Experimental: Arm 2: Livmoniplimab Dose A + Budigalimab<br>Participants will receive Livmoniplimab Dose A in combination with budigalimab, as part of an approximately 2 year treatment period. | Drug: Budigalimab<br>* Intravenous (IV) Infusion<br>* Other names: ABBV-181;Drug: Livmoniplimab<br>* Intravenous (IV) Infusion<br>* Other names: ABBV-151;|
| Experimental: Arm 3: Livmoniplimab Dose B + Budigalimab<br>Participants will receive Livmoniplimab Dose B in combination with budigalimab, as part of an approximately 2 year treatment period. | Drug: Budigalimab<br>* Intravenous (IV) Infusion<br>* Other names: ABBV-181;Drug: Livmoniplimab<br>* Intravenous (IV) Infusion<br>* Other names: ABBV-151;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) per Investigator | BOR is defined as a subject 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. | Through Study Completion, Up to Approximately 27 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DOR) per Investigator | 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. | Through Study Completion, Up to Approximately 27 Months | 
| Number of Participants with Progression-free Survival (PFS) | 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. | Through Study Completion, Up to Approximately 27 Months | 
| Overall Survival (OS) | OS is defined as the time from randomization until death from any cause. | Through Study Completion, Up to Approximately 27 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sorafenib, Livmoniplimab, Budigalimab, ABBV-181, ABBV-151, Cancer, Hepatocellular Carcinoma, Lenvatinib