A Phase 1b Study to Evaluate the Safety and Pharmacokinetics of Livmoniplimab in Combination With Budigalimab in Chinese Subjects With Locally Advanced or Metastatic Child-Pugh A Hepatocellular Carcinoma Who Have Progressed After a First-Line Regimen That Includes an Immune Checkpoint Inhibitor
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 3
- Locations
- 22
- Primary Endpoint
- Maximum Plasma Concentration (Cmax) of Livmoniplimab and Budigalimab
Study Overview
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 assess adverse events and how livmoniplimab in combination with budigalimab moves through the body in adult Chinese participants with Locally Advanced or metastatic Child-Pugh A Hepatocellular Carcinoma (HCC).
Livmoniplimab is an investigational drug being developed for the treatment of HCC. There are 2 stages to this study. Stage 1 is a safety run-in. There are 2 treatment arms in stage 1 and participants will receive escalating doses of Livmoniplimab in combination with budigalimab (fixed dose). Stage 2 is dose expansion. There are 2 treatment arms in stage 2 and participants will receive Livmoniplimab in combination with budigalimab in multiple doses. Approximately 20 adult participants will be enrolled in the study across 15 sites in China.
In part 1 (dose escalation), participants will be intravenously infused with escalating doses of livmoniplimab in combination with budigalimab every 3 weeks. In part 2 (dose expansion), participants will be intravenously infused with livmoniplimab in combination with budigalimab in multiple doses every 3 weeks. The estimated duration of the study is up to 2 years.
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, and scans.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Locally advanced or metastatic and/or unresectable HCC
- •Child-Pugh A
- •Barcelona Clinic Liver Cancer stage B or C
- •Eastern Cooperative Oncology Group (ECOG) Perfromance Status of 0-1
- •Received an immune checkpoint inhibitor in 1L HCC treatment regimen
- •Adequate hematologic and end-organ function
Exclusion Criteria
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases as outlined in the protocol.
- •History of malignancy other than HCC within 5 years prior to screening, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%).
- •History of autoimmune, immune deficiency, or inflammatory disorders including, but not limited to, inflammatory bowel disease, systemic lupus erythematosus, sarcoidosis, Wegener syndrome, rheumatoid arthritis, antiphospholipid antibody syndrome, Guillain-Barre syndrome, or multiple sclerosis
- •History of clinically significant conditions such as but not limited to the following: renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, pulmonary, or hepatic disease within the last 6 months that in Investigator's opinion, would adversely affect the subject's participation in the study.
Arms & Interventions
Stage 1: Cohort 1 Livmoniplimab + Budigalimab Dose A
Participants will receive livmoniplimab Dose A in combination with budigalimab every 3 weeks for approximately 2 years.
Intervention: Livmoniplimab (Drug)
Stage 1: Cohort 1 Livmoniplimab + Budigalimab Dose A
Participants will receive livmoniplimab Dose A in combination with budigalimab every 3 weeks for approximately 2 years.
Intervention: Budigalimab (Drug)
Stage 2: Cohort 2 Livmoniplimab + Budigalimab Dose B
Participants will receive livmoniplimab Dose B in combination with budigalimab every 3 weeks for approximately 2 years.
Intervention: Livmoniplimab (Drug)
Stage 2: Cohort 2 Livmoniplimab + Budigalimab Dose B
Participants will receive livmoniplimab Dose B in combination with budigalimab every 3 weeks for approximately 2 years.
Intervention: Budigalimab (Drug)
Outcomes
Primary Outcomes
Maximum Plasma Concentration (Cmax) of Livmoniplimab and Budigalimab
Time Frame: Up to Approximately 2 Years
Maximum Plasma Concentration (Cmax) of livmoniplimab and Budigalimab
Percentage of Participants With Adverse Events (AE)
Time Frame: Up to Approximately 2 Years
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Number of Participants with Dose-Limiting Toxicities (DLT)
Time Frame: Up to Approximately 2 Years
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Area Under the Serum Concentration Versus Time Curve (AUC) of Livmoniplimab and Budigalimab
Time Frame: Up to Approximately 2 Years
AUC of livmoniplimab and Budigalimab
Secondary Outcomes
- Overall survival (OS)(Up to Approximately 2 Years)
- Antidrug Antibody (ADA)(Up to Approximately 2 Years)
- Duration of response (DOR) for Participants with Confirmed CR/PR(Up to Approximately 2 Years)
- Best Overall Response (BOR) for Participants with Confirmed CR/PR per RECIST v1.1(Up to Approximately 2 Years)
- Progression-free survival (PFS)(Up to Approximately 2 Years)
- Neutralizing Antidrug Antibody (nADA)(Up to Approximately 2 Years)