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)
- Conditions
- Hepatocellular Carcinoma
- Interventions
- Registration Number
- NCT06109272
- Lead Sponsor
- AbbVie
- 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 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 660
- 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.
- Prior systemic therapy for HCC.
- Symptomatic, untreated, or actively progressing CNS metastases.
- History of malignancy other than HCC.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Stage 1: Cohort 1 Budigalimab Participants will receive livmoniplimab Dose 1 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met. Stage 1: Cohort 2 Livmoniplimab Participants will receive livmoniplimab Dose 2 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met. Stage 1: Cohort 2 Budigalimab Participants will receive livmoniplimab Dose 2 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met. Stage 1: Cohort 1 Livmoniplimab Participants will receive livmoniplimab Dose 1 in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met. Stage 1: Cohort 3 - Group 2 (Control) Tremelimumab Participants will receive a single dose of tremelimumab in combination with durvalumab every four weeks until disease progression or until discontinuation criteria are met. Stage 2: Arm 1 Budigalimab Participants will receive livmoniplimab (optimized dose) in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met. Stage 2: Arm 2 (Control) Tremelimumab Participants will receive a single dose of tremelimumab in combination with durvalumab every 4 weeks until disease progression or until discontinuation criteria are met. Stage 2: Arm 1 Livmoniplimab Participants will receive livmoniplimab (optimized dose) in combination with budigalimab every 3 weeks until disease progression or until discontinuation criteria are met. Stage 1: Cohort 3 - Group 1 (Control) Atezolizumab Participants will receive atezolizumab in combination with bevacizumab every 3 weeks until disease progression or until discontinuation criteria are met. Stage 1: Cohort 3 - Group 1 (Control) Bevacizumab Participants will receive atezolizumab in combination with bevacizumab every 3 weeks until disease progression or until discontinuation criteria are met. Stage 1: Cohort 3 - Group 2 (Control) Durvalumab Participants will receive a single dose of tremelimumab in combination with durvalumab every four weeks until disease progression or until discontinuation criteria are met. Stage 2: Arm 2 (Control) Durvalumab Participants will receive a single dose of tremelimumab in combination with durvalumab every 4 weeks until disease progression or until discontinuation criteria are met.
- Primary Outcome Measures
Name Time Method 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
Name Time Method Stage 1: Maximum Plasma Concentration (Cmax) of Livmoniplimab and Budigalimab Through Study Completion, Up to Approximately 56 Months Cmax 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.
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.
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: 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.
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.
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: 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 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 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.
Trial Locations
- Locations (37)
Hopital Beaujon /ID# 256551
🇫🇷Clichy, Ile-de-France, France
CHU Grenoble - Hopital Michallon /ID# 256627
🇫🇷La Tronche, Isere, France
City of Hope /ID# 261468
🇺🇸Duarte, California, United States
City of Hope at Orange County Lennar Foundation Cancer Center /ID# 261669
🇺🇸Irvine, California, United States
UC Irvine /ID# 255673
🇺🇸Orange, California, United States
The University of Chicago Medical Center /ID# 255674
🇺🇸Chicago, Illinois, United States
Alliance for Multispecialty Research LLC Kansas City Oncology /ID# 256830
🇺🇸Merriam, Kansas, United States
Norton Cancer Institute /ID# 260775
🇺🇸Louisville, Kentucky, United States
Henry Ford Hospital /ID# 255803
🇺🇸Detroit, Michigan, United States
Metro Minnesota Community Oncology Research Consortium (MMCORC) /ID# 256041
🇺🇸Saint Louis Park, Minnesota, United States
Washington University-School of Medicine /ID# 255720
🇺🇸Saint Louis, Missouri, United States
Texas Oncology - Abilene - Antilley Road /ID# 265820
🇺🇸Abilene, Texas, United States
Texas Oncology - Dallas - Worth Street /ID# 265806
🇺🇸Dallas, Texas, United States
Baylor Scott and White Research Institute /ID# 260853
🇺🇸Dallas, Texas, United States
Oncology and Hematology Associates of Southwest Virginia /ID# 265834
🇺🇸Roanoke, Virginia, United States
Hôpital Avicenne /ID# 266005
🇫🇷Bobigny, Ile-de-France, France
Institut Gustave Roussy /ID# 258460
🇫🇷Villejuif Cedex, Val-de-Marne, France
IRCCS AOU di Bologna - Policlinico Sant'Orsola-Malpighi /ID# 256412
🇮🇹Bologna, Emilia-Romagna, Italy
IRCCS Istituto Clinico Humanitas /ID# 256684
🇮🇹Rozzano, Lombardia, Italy
IRCCS Ospedale San Raffaele /ID# 256404
🇮🇹Milan, Milano, Italy
P.O. Ospedale del Mare /ID# 256410
🇮🇹Naples, Napoli, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 265506
🇮🇹Rome, Roma, Italy
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone /ID# 256681
🇮🇹Palermo, Italy
Fondazione Policlinico Universitario Campus Bio-Medico /ID# 256895
🇮🇹Roma, Italy
Puerto Rico Medical Research Center /ID# 262362
🇵🇷Hato Rey, Puerto Rico
Hospital Universitario Marques de Valdecilla /ID# 255769
🇪🇸Santander, Cantabria, Spain
Hospital Universitario Reina Sofia /ID# 255779
🇪🇸Córdoba, Cordoba, Spain
Hospital Universitario Puerta de Hierro - Majadahonda /ID# 255778
🇪🇸Majadahonda, Madrid, Spain
Hospital Universitario Vall d'Hebron /ID# 255771
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Maranon /ID# 255772
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio /ID# 255776
🇪🇸Sevilla, Spain
Hospital Universitario Miguel Servet /ID# 255774
🇪🇸Zaragoza, Spain
National Taiwan University Hospital /ID# 256168
🇨🇳Taipei City, Taipei, Taiwan
China Medical University Hospital /ID# 256764
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital /ID# 259405
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital /ID# 256766
🇨🇳Tainan, Taiwan
Taipei Veterans General Hosp /ID# 256169
🇨🇳Taipei, Taiwan