Trial: A Study to Assess the Dose, Adverse Eve…

Trial Details

Sponsor: AbbVie (industry)

Phase: 2/3

Start date: Jan. 11, 2024

Planned enrollment: 660

Trial ID: NCT06109272

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

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.

Investigational Drug AI Analysis

Show for: Budigalimab (PR-1648817, ABBV-181)

Overview

Budigalimab, also known as ABBV-181 or PR-1648817, is an investigational humanized monoclonal antibody targeting the programmed cell death protein 1 (PD-1) receptor. It is being developed for the treatment of various advanced solid tumors.

Mechanism of Action

Budigalimab functions by binding to the PD-1 receptor on T cells, thereby inhibiting its interaction with its ligands, PD-L1 and PD-L2. This blockade enhances T-cell activity, promoting an immune response against tumor cells.

Efficacy

In a phase I clinical trial involving patients with previously treated advanced solid tumors, budigalimab demonstrated antitumor activity. Among 59 patients in the dose escalation cohort, four partial responses were observed:

Renal Cell Carcinoma: One confirmed partial response in a patient with 15% PD-L1 tumor cell staining.
Non-Small Cell Lung Cancer (NSCLC): One unconfirmed partial response in a patient with 70% PD-L1 tumor cell staining.
Cholangiocarcinoma: One unconfirmed partial response in a patient with unknown PD-L1 status.
Leiomyosarcoma: One confirmed partial response in a patient with 0% PD-L1 tumor cell staining.

No responses were reported in the multihistology expansion cohort. (pubmed.ncbi.nlm.nih.gov)

Another phase I study focusing on patients with head and neck squamous cell carcinoma (HNSCC) and NSCLC reported objective response rates of 13% and 19%, respectively. Median progression-free survival was 3.6 months for HNSCC and 1.9 months for NSCLC. (pmc.ncbi.nlm.nih.gov)

Safety

Budigalimab was generally well-tolerated. In the dose escalation study, immune-related adverse events occurred in 18.6% of patients, with only 1.7% experiencing grade ≥3 events. No treatment-related grade 5 adverse events were reported. (pubmed.ncbi.nlm.nih.gov)

In the HNSCC and NSCLC cohorts, the most common treatment-related adverse events included hypothyroidism, diarrhea, and pruritus. Grade ≥3 treatment-emergent adverse events were observed in 22% of HNSCC patients and 13% of NSCLC patients, with anemia being the most frequent. (pmc.ncbi.nlm.nih.gov)

Show for: Livmoniplimab (ARGX-115, ABBV-151)

HealthScout AI Analysis

Goal: Evaluate optimized dosing, safety, and antitumor efficacy of the investigational combination of livmoniplimab plus budigalimab versus contemporary first-line immunotherapy standards in untreated, locally advanced or metastatic/unresectable HCC.

Patients: Adults with histologically/cytologically confirmed, or clinically diagnosed (per AASLD in cirrhosis) HCC, BCLC stage B or C, Child-Pugh A or B7, ECOG 0–1, and no prior systemic therapy. Exclusions include symptomatic/untreated/actively progressing CNS metastases and history of other malignancies.

Design: Global, randomized, multicenter Phase 2/3 study. Stage 1 (dose-optimization/selection): three-arm randomization (1:1:1) comparing two dose levels of livmoniplimab plus budigalimab versus investigator’s choice of atezolizumab–bevacizumab or single-dose tremelimumab plus durvalumab. Stage 2 (confirmatory): two-arm randomization (1:1) of optimized-dose livmoniplimab plus budigalimab versus tremelimumab plus durvalumab. Treatment continues until progression or discontinuation criteria; total study duration approximately 56 months.

Treatments: Investigational: Livmoniplimab plus budigalimab administered IV every 3 weeks. Livmoniplimab (ABBV-151) is a humanized IgG4-kappa monoclonal antibody targeting the GARP/TGF-β1 complex to block GARP-mediated activation of latent TGF-β1, aiming to counter tumor-associated Treg immunosuppression. In a Phase 1 trial in advanced solid tumors, livmoniplimab monotherapy showed no objective responses, but the combination with the anti–PD-1 antibody budigalimab had a manageable safety profile and demonstrated activity, including approximately 33% response in PD-1–naïve HCC and 16% in PD-1–experienced urothelial cancer; grade 3–4 AEs occurred in about half of patients with roughly 14% drug-related. Budigalimab is a humanized IgG1 anti–PD-1 antibody engineered to minimize Fc-mediated effector function; early-phase studies showed dose-proportional PK, rapid PD-1 target saturation, and response rates consistent with the PD-1 class in selected tumors with a safety profile similar to other PD-1 inhibitors. Controls: Atezolizumab plus bevacizumab every 3 weeks, a standard first-line regimen in unresectable HCC; or single-dose tremelimumab with durvalumab every 4 weeks, an approved first-line immunotherapy option in HCC.

Outcomes: Primary endpoints: Stage 1 best overall response (RECIST 1.1, investigator-assessed) to select the optimized dose; Stage 2 overall survival. Key secondary endpoints include progression-free survival (Stage 1 investigator-assessed; Stage 2 BICR), duration of response, overall survival in Stage 1, safety and adverse events, pharmacokinetics of both antibodies (Cmax, Tmax, AUC) in Stage 1, and patient-reported outcomes assessing pain and fatigue (EORTC QLQ-HCC18) and physical function and global health status/quality of life (EORTC QLQ-C30) through Week 12.

Burden on patient: Moderate to high. Participants will have frequent IV infusions every 3 weeks in experimental arms or every 3–4 weeks in control arms, imaging per protocol to assess response, and standard safety labs. Stage 1 includes pharmacokinetic sampling for both antibodies, increasing blood-draw frequency and visit duration, particularly in early cycles. Eligibility requires baseline staging, liver function assessments, and ongoing monitoring consistent with HCC immunotherapy trials; additional PRO questionnaires add minimal time burden. Travel to study sites every 3–4 weeks over potentially prolonged treatment and the intensity of assessments exceed many routine care settings, contributing to higher overall burden.

Eligibility

Show Criteria

No email / 254-724-1054

Status: Recruiting

Oncology and Hematology Associates of Southwest Virginia /ID# 265834

Roanoke, Virginia, 98684, United States

No email / No phone

Status: Recruiting

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

Trial Details

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: Budigalimab (PR-1648817, ABBV-181)

Overview

Mechanism of Action

Efficacy

Safety

Further Reading

Show for: Livmoniplimab (ARGX-115, ABBV-151)

Overview

Mechanism of Action

Efficacy

Safety

Further Reading

HealthScout AI Analysis

Eligibility

Show Criteria

Sites (37)

Hopital Beaujon /ID# 256551

Hôpital Avicenne /ID# 266005

CHU Grenoble - Hopital Michallon /ID# 256627

Institut Gustave Roussy /ID# 258460

IRCCS Istituto Clinico Humanitas /ID# 256684

IRCCS Ospedale San Raffaele /ID# 256404

P.O. Ospedale del Mare /ID# 256410

Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 265506

Fondazione Policlinico Universitario Campus Bio-Medico /ID# 256895

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone /ID# 256681

IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 256412

Puerto Rico Medical Research Center /ID# 262362

Hospital Universitario Marques de Valdecilla /ID# 255769

Hospital Universitario Reina Sofia /ID# 255779

Hospital Universitario Puerta de Hierro - Majadahonda /ID# 255778

Hospital Universitario Vall d'Hebron /ID# 255771

Hospital General Universitario Gregorio Maranon /ID# 255772

Hospital Universitario Virgen del Rocio /ID# 255776

Hospital Universitario Miguel Servet /ID# 255774

National Taiwan University Hospital /ID# 256168

Taipei Veterans General Hosp /ID# 256169

China Medical University Hospital /ID# 256764

Taichung Veterans General Hospital /ID# 259405

National Cheng Kung University Hospital /ID# 256766

City of Hope /ID# 261468

UC Irvine /ID# 255673

City of Hope at Orange County Lennar Foundation Cancer Center /ID# 261669

The University of Chicago Medical Center /ID# 255674

Alliance for Multispecialty Research LLC Kansas City Oncology /ID# 256830

Norton Cancer Institute /ID# 260775

Henry Ford Hospital /ID# 255803

Metro Minnesota Community Oncology Research Consortium (MMCORC) /ID# 256041

Washington University-School of Medicine /ID# 255720

Texas Oncology - Dallas - Worth Street /ID# 265806

Texas Oncology - Abilene - Antilley Road /ID# 265820

Baylor Scott and White Research Institute /ID# 260853

Oncology and Hematology Associates of Southwest Virginia /ID# 265834