BO-112 and Pembrolizumab for the Treatment of PD-1/PD-L1 Refractory Liver Cancer

Advanced Hepatocellular Carcinoma Clinical Trial

Official title: Pilot Feasibility Study of Intratumoral BO-112 in Combination With Pembrolizumab for Advanced Hepatocellular Carcinoma

Status Terminated

Clinical Trial Summary

This early phase I trial evaluates the side effects of BO-112 and pembrolizumab and how well they work in treating patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C liver cancer. Immunotherapy with BO-112, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving BO-112 and pembrolizumab may help treat patients with liver cancer.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine the early efficacy and safety for the combination of intratumoral nanoplexed poly I:C BO-112 (BO-112) in combination with pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) who have progressed on prior anti-PD-1/PD-L1 therapy.

SECONDARY OBJECTIVES:

I. To further elucidate efficacy endpoints of the combination the combination of BO-112 with pembrolizumab.

II. To demonstrate the efficacy of BO-112 from its hypothesized mechanism of action.

CORRELATIVE RESEARCH OBJECTIVES:

I. Peripheral blood will be collected to assess changes in circulating cluster of differentiation 4 (CD4+), cluster of differentiation 8 (CD8+), natural killer (NK), and dendritic cells.

II. Peripheral blood will be collected to assess leukocyte expression of interferon beta induced genes in conjunction with intratumoral studies to demonstrate increased intratumoral interferon beta and other hypothesized biomarkers.

III. A baseline biopsy will be collected on cycle 1 day 1 and at cycle 2 day 15 (done at the same time as intratumoral injection).

IIIa. From these biopsies, intratumoral CD4+, CD8+ expression and cluster of differentiation 56 (CD56+) expression (NK cells) will be measured by immunohistochemistry on the baseline biopsy and the biopsy on cycle 2 day 15.

IIIb. Myeloid dendritic cells will be assessed by flow cytometry, as their activity correlates with Toll-like receptor 3 (TLR3) activation.

IIIc. Percentage of cells with apoptosis and necrosis will be assessed. IIId. The tumor microenvironment will be assessed by ribonucleic acid (RNA) expression profiling with nCounter Pancancer Immune Profiling Panel given its extensive validation to date.

IV. To assess the potential of immune-related Response Evaluation Criteria in Solid Tumors (RECIST) (iRECIST) to determine disease control as compared to RECIST 1.1.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of odd number cycles. Patients also receive BO-112 by intratumoral injection on day 1, 8, and 15 of cycle 1, and day 15 of subsequent cycles. Treatment repeats every 3 weeks for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 8 weeks for 1 year, and then every 12 weeks thereafter. ;

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• BCLC Stage B Hepatocellular Carcinoma
• BCLC Stage C Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular
• Refractory Hepatocellular Carcinoma

• NCT number: NCT04777708
• Study type: Interventional
• Source: Jonsson Comprehensive Cancer Center
• Status: Terminated
• Phase: Early Phase 1
• Start date: October 13, 2021
• Completion date: March 13, 2023