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Spatial immuno-oncology protein abundance profiles in hepatocellular carcinoma tissues from patients treated with bavituximab and pembrolizumab

ABSTRACT: Immune checkpoint inhibitors (ICIs) targeting PD-1/L1 have modest efficacy in hepatocellular carcinoma (HCC) as single agents, but combination regimens have demonstrated increased clinical benefit at the expense of treatment toxicities. Exposed phosphatidylserine suppresses the innate immune response in the tumor microenvironment (TME). Targeting phosphatidylserine does not induce tumor responses in the clinical setting when used as monotherapy or in combination with cytotoxic and targeted therapies, but may induce pro-inflammatory and –immune stimulating effects that enhance ICI activity. This hypothesis was tested in a single-arm phase 2 trial evaluating bavituximab, a phosphatidylserine targeting antibody, plus pembrolizumab in patients with unresectable HCC who had not received prior systemic treatments (ClinicalTrials.gov ID: NCT03519997). The primary end point was investigator-assessed objective response rate (ORR) among evaluable patients, and secondary end points included progression-free survival (PFS) and the incidence of adverse events. Among 28 evaluable patients, the ORR was 32.1%, including 2 complete responses, and a disease control rate of 64.3%. Median PFS was 6.3 months (95% CI, 1.3-11.3 months). Treatment related adverse events of any grade occurred in 45.7% of patients with grade 3 or 4 adverse events occurring in 14.3% of patients. Exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the expression of smooth muscle actin and immune checkpoints in stroma was associated with tumor response. An RNA-based TME assay which distinguishes immune-rich of inflammatory tumors was also shown to be predictive of ORR. These results suggest that targeting phosphatidylserine may lead to synergistic effects with ICIs without increasing toxicity rates, and future studies on this therapeutic strategy may be guided by biomarkers characterizing the TME.

ORGANISM(S): Homo sapiens

PROVIDER: GSE242154 | GEO | 2024/02/08

REPOSITORIES: GEO

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Spatial immuno-oncology protein abundance profiles in hepatocellular carcinoma tissues from patients treated with bavituximab and pembrolizumab

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