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

Overview

Budigalimab (ABBV-181; PR-1648817) is an investigational humanized IgG1 monoclonal antibody targeting programmed cell death protein 1 (PD-1). It has been studied as monotherapy and in combination regimens for advanced cancers, and at substantially lower doses as a potential immune-based intervention for HIV-1. (pmc.ncbi.nlm.nih.gov)

Mechanism of action

Budigalimab binds PD-1 and blocks its interaction with PD-L1 and PD-L2, relieving inhibitory signaling and potentially restoring T-cell activity. Its Fc region contains mutations intended to reduce Fc-receptor interactions and associated effector functions. Phase 1 pharmacodynamic studies found rapid, sustained PD-1 receptor saturation at the oncology doses evaluated. (pmc.ncbi.nlm.nih.gov)

Efficacy

In a phase 1 monotherapy expansion study, 81 checkpoint-inhibitor-naive patients received 250 mg every two weeks or 500 mg every four weeks:

• Head and neck squamous-cell carcinoma: confirmed objective response rate (ORR) was 13% among 40 evaluable patients; median response duration was 9.4 months and median progression-free survival (PFS) was 3.6 months.
• Non-small-cell lung cancer: confirmed ORR was 19% among 37 evaluable patients, including one complete response; median response duration was 10.1 months and median PFS was 1.9 months. (pmc.ncbi.nlm.nih.gov)

Earlier mixed-tumor dose-escalation and expansion cohorts reported four responses during dose escalation but none in the multihistology expansion cohort. (pmc.ncbi.nlm.nih.gov)

In a small randomized phase 1b HIV-1 study, six of 11 participants receiving four 10-mg doses every two weeks experienced delayed viral rebound and/or at least six weeks of low-level viral control during analytical treatment interruption. Two maintained HIV-1 RNA below 200 copies/mL without antiretroviral therapy through study end at 204 and 252 days. These exploratory findings are based on very small numbers and do not establish efficacy. (pmc.ncbi.nlm.nih.gov)

Safety

In the cancer expansion cohorts, investigator-attributed treatment-related adverse events occurred in 63% of patients with head and neck cancer and 58% with lung cancer. Common events included hypothyroidism, diarrhea, pruritus and fatigue. Grade 3 or higher treatment-related events occurred in 10% and 13%, respectively; no treatment-related deaths were reported. (pmc.ncbi.nlm.nih.gov)

In the 41-participant HIV study, most adverse events were grade 1–2. No grade 3 or higher treatment-related events, treatment-related serious events or deaths occurred. Two participants developed reversible grade 1 immune-related thyroid disorders. (pmc.ncbi.nlm.nih.gov)

Further reading

• First-in-human oncology study in NSCLC and head and neck cancer
• Phase 1 dose selection, pharmacokinetics and mixed-solid-tumor results
• Randomized phase 1b HIV-1 study
• NCI Drug Dictionary entry

Last updated: Sep 2026

Overview

Livmoniplimab (ARGX-115; ABBV-151) is an investigational intravenous monoclonal antibody being developed for solid tumors, principally in combination with the anti–PD-1 antibody budigalimab. Published human evidence consists mainly of an early-phase, nonrandomized study; randomized trials are ongoing, so clinical benefit has not been established. (pmc.ncbi.nlm.nih.gov)

Mechanism of action

Livmoniplimab binds the complex formed by glycoprotein-A repetitions predominant protein (GARP/LRRC32) and latent transforming growth factor beta-1 (TGF-β1). GARP presents latent TGF-β1 on regulatory T cells and other cells, enabling its activation. Livmoniplimab stabilizes this complex and prevents release of active TGF-β1, with the aim of reducing TGF-β–mediated immune suppression in the tumor microenvironment without broadly blocking all TGF-β signaling. (pmc.ncbi.nlm.nih.gov)

Efficacy

In the first-in-human phase 1 dose-escalation study, 57 patients with advanced solid tumors received livmoniplimab alone (n=23) or with budigalimab (n=34). No objective responses occurred with monotherapy. Combination therapy produced a 15% objective response rate (ORR) and a median response duration of 8.4 months. These findings were preliminary and came from a heterogeneous, uncontrolled population. (pmc.ncbi.nlm.nih.gov)

In a phase 1 expansion cohort of previously treated advanced urothelial carcinoma, 45 patients were response-evaluable. The confirmed ORR was 18%; median restricted mean response duration was 7.9 months, and median progression-free survival was 1.8 months. (ascopubs.org)

A separate four-patient subgroup with metastatic ovarian granulosa-cell tumors had three partial responses (ORR 75%) and disease control in all four patients. One response lasted approximately 2.5 years. The very small sample size makes this result hypothesis-generating rather than definitive. (aacrjournals.org)

Safety

In phase 1 dose escalation, treatment-emergent adverse events occurred in 96% of monotherapy patients and included fatigue, anemia and nausea. Grade 3–4 events occurred in 39%. With livmoniplimab plus budigalimab, common events included pruritus, fatigue, nausea and anemia; 68% experienced grade 3–4 events. One dose-limiting elevation of alanine aminotransferase occurred, the maximum tolerated dose was not reached, and no treatment-related deaths were reported. (pmc.ncbi.nlm.nih.gov)

In the urothelial-cancer expansion, all 48 patients experienced a treatment-emergent adverse event and 48% had grade 3–4 events. Pruritus was the most common event; 11 patients died during the study, but none of the deaths was considered related to livmoniplimab or budigalimab. (ascopubs.org)

Further reading

• Peer-reviewed first-in-human phase 1 results
• Urothelial-cancer expansion abstract
• Ovarian granulosa-cell tumor abstract
• Foundational study of GARP-mediated TGF-β activation
• ClinicalTrials.gov: first-in-human study NCT03821935

Last updated: Sep 2026

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.