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)

Hepatocellular Carcinoma Clinical Trial

— LIVIGNO-2  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06109272
• Other study ID #: M24-052
• Secondary ID: 2023-504600-28-0
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 11, 2024
• Est. completion date: September 6, 2030

Study information

• Verified date: June 2024
• Source: AbbVie
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 660
• Est. completion date: September 6, 2030
• Est. primary completion date: September 6, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Livmoniplimab
Intravenous (IV) Solution
• Budigalimab
Intravenous (IV) Solution
• Durvalumab
Intravenous (IV) Solution
• Atezolizumab
Intravenous (IV) Solution
• Bevacizumab
Intravenous (IV) Solution
• Tremelimumab
Intravenous (IV) Solution

Locations

Country	Name	City	State
France	Hopital Beaujon /ID# 256551	Clichy	Ile-de-France
France	CHU Grenoble - Hopital Michallon /ID# 256627	La Tronche	Isere
Spain	Hospital Universitario Vall d'Hebron /ID# 255771	Barcelona
Spain	Hospital Universitario Reina Sofia /ID# 255779	Córdoba	Cordoba
Spain	Hospital Universitario Marques de Valdecilla /ID# 255769	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocio /ID# 255776	Sevilla
Spain	Hospital Universitario Miguel Servet /ID# 255774	Zaragoza
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	National Taiwan University Hospital /ID# 256168	Taipei City	Taipei
United States	The University of Chicago Medical Center /ID# 255674	Chicago	Illinois
United States	Henry Ford Hospital /ID# 255803	Detroit	Michigan
United States	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	Norton Cancer Institute /ID# 260775	Louisville	Kentucky
United States	Alliance for Multispecialty Research LLC Kansas City Oncology /ID# 256830	Merriam	Kansas
United States	UC Irvine /ID# 255673	Orange	California
United States	Washington University-School of Medicine /ID# 255720	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium (MMCORC) /ID# 256041	Saint Louis Park	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  France,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage 1: Best Overall Response (BOR) per Investigator	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.	Through Study Completion, Up to Approximately 56 Months
Primary	Stage 2: Overall Survival (OS)	OS is defined as the time from randomization until death from any cause	Through Study Completion, Up to Approximately 56 Months
Secondary	Stage 1: 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 56 Months
Secondary	Stage 1: 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 56 Months
Secondary	Stage 1: Overall Survival (OS)	OS is defined as the time from randomization until death from any cause.	Through Study Completion, Up to Approximately 56 Months
Secondary	Stage 1: Number of Participants with Adverse Events (AEs)	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.	Through Study Completion, Up to Approximately 56 Months
Secondary	Stage 1: Maximum Plasma Concentration (Cmax) of Livmoniplimab and Budigalimab	Cmax of livmoniplimab and budigalimab.	Through Study Completion, Up to Approximately 56 Months
Secondary	Stage 1: Time to Cmax (Tmax) of Livmoniplimab and Budigalimab	Tmax of livmoniplimab and budigalimab.	Through Study Completion, Up to Approximately 56 Months
Secondary	Stage 1: Area Under the Serum Concentration Versus Time Curve (AUC) of Livmoniplimab and Budigalimab	AUC of livmoniplimab and budigalimab.	Through Study Completion, Up to Approximately 56 Months
Secondary	Stage 2: 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 blinded independent central review (BICR) or death from any cause, whichever occurs first.	Through Study Completion, Up to Approximately 56 Months
Secondary	Stage 2: Best Overall Response (BOR) of Complete Response (CR)/Partial Response (PR) per BICR	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.	Through Study Completion, Up to Approximately 56 Months
Secondary	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)	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.	Baseline to Week 12
Secondary	Change from Baseline in the Fatigue Domain of the EORTC QLQ-HCC18	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.	Baseline to Week 12
Secondary	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)	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.	Baseline to Week 12
Secondary	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	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.	Baseline to Week 12

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