Clinical trial NCT06109272: 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)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
Livmoniplimab
ABBV-151
budigalimab
ABBV-181
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2023-10-31
Enrollment: 660
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Stage 1: Best Overall Response (BOR) per Investigator
timeFrame: Through Study Completion, Up to Approximately 56 Months
measure: Stage 2: Overall Survival (OS)
timeFrame: Through Study Completion, Up to Approximately 56 Months
Secondary outcomes:
measure: Stage 1: Number of Participants with Progression-Free Survival (PFS)
timeFrame: Through Study Completion, Up to Approximately 56 Months
measure: Stage 1: Duration of Response (DOR) per Investigator
timeFrame: Through Study Completion, Up to Approximately 56 Months
measure: Stage 1: Overall Survival (OS)
timeFrame: Through Study Completion, Up to Approximately 56 Months
measure: Stage 1: Number of Participants with Adverse Events (AEs)
timeFrame: Through Study Completion, Up to Approximately 56 Months
measure: Stage 1: Maximum Plasma Concentration (Cmax) of Livmoniplimab and Budigalimab
timeFrame: Through Study Completion, Up to Approximately 56 Months
measure: Stage 1: Time to Cmax (Tmax) of Livmoniplimab and Budigalimab
timeFrame: Through Study Completion, Up to Approximately 56 Months
measure: Stage 1: Area Under the Serum Concentration Versus Time Curve (AUC) of Livmoniplimab and Budigalimab
timeFrame: Through Study Completion, Up to Approximately 56 Months
measure: Stage 2: Number of Participants with Progression-Free Survival (PFS)
timeFrame: Through Study Completion, Up to Approximately 56 Months
measure: Stage 2: Best Overall Response (BOR) of Complete Response (CR)/Partial Response (PR) per BICR
timeFrame: Through Study Completion, Up to Approximately 56 Months
measure: 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)
timeFrame: Baseline to Week 12
measure: Change from Baseline in the Fatigue Domain of the EORTC QLQ-HCC18
timeFrame: Baseline to Week 12
measure: 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)
timeFrame: Baseline to Week 12
measure: 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
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope /ID# 261468
state: California
city: Irvine
country: United States
facility: City of Hope at Orange County Lennar Foundation Cancer Center /ID# 261669
state: California
city: Orange
country: United States
facility: UC Irvine /ID# 255673
state: California
city: Chicago
country: United States
facility: The University of Chicago Medical Center /ID# 255674
state: Illinois
city: Merriam
country: United States
facility: Alliance for Multispecialty Research LLC Kansas City Oncology /ID# 256830
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute /ID# 260775
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Hospital /ID# 255803
state: Michigan
city: Saint Louis Park
country: United States
facility: Metro Minnesota Community Oncology Research Consortium (MMCORC) /ID# 256041
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 255720
state: Missouri
city: Abilene
country: United States
facility: Texas Oncology - Abilene - Antilley Road /ID# 265820
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas - Worth Street /ID# 265806
state: Texas
city: Dallas
country: United States
facility: Baylor Scott and White Research Institute /ID# 260853
state: Texas
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia /ID# 265834
state: Virginia
city: Bobigny
country: France
facility: Hôpital Avicenne /ID# 266005
state: Ile-de-France
city: Clichy
country: France
facility: Hopital Beaujon /ID# 256551
state: Ile-de-France
city: La Tronche
country: France
facility: CHU Grenoble - Hopital Michallon /ID# 256627
state: Isere
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy /ID# 258460
state: Val-de-Marne
city: Bologna
country: Italy
facility: IRCCS AOU di Bologna - Policlinico Sant'Orsola-Malpighi /ID# 256412
state: Emilia-Romagna
city: Rozzano
country: Italy
facility: IRCCS Istituto Clinico Humanitas /ID# 256684
state: Lombardia
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele /ID# 256404
state: Milano
city: Naples
country: Italy
facility: P.O. Ospedale del Mare /ID# 256410
state: Napoli
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 265506
state: Roma
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone /ID# 256681
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Campus Bio-Medico /ID# 256895
city: Hato Rey
country: Puerto Rico
facility: Puerto Rico Medical Research Center /ID# 262362
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla /ID# 255769
state: Cantabria
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia /ID# 255779
state: Cordoba
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda /ID# 255778
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 255771
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon /ID# 255772
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 255776
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet /ID# 255774
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 256168
state: Taipei
city: Taichung
country: Taiwan
facility: China Medical University Hospital /ID# 256764
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital /ID# 259405
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital /ID# 256766
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hosp /ID# 256169
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: