Is Targeting Membranous Phosphatidylserine Effective in Unresectable HCC?

A single-arm, phase 2 study from David Hsiehchen, MD, and colleagues investigated the potential benefits of the phosphatidylserine-targeting antibody bavituximab plus pembrolizumab in the treatment of unresectable hepatocellular carcinoma (HCC).

The study was published in Nature Communications.

Researchers proposed that targeting membranous phosphatidylserine may improve immunotherapy activity in patients with unresectable HCC by creating proinflammatory and immune-stimulating effects.

The trial included 15 patients in the first stage and 13 patients in the second stage, with the primary end point of investigator-determined overall response rate (ORR).

The ORR for the 28 evaluable patients was 32.1%, which included 2 complete responses (CRs) and 7 partial responses (PRs). The disease control rate, noting CRs, PRs, and stable disease, was 64.3%, while the median time to response was 2.1 months and the median duration of response was 13.3 months. At the data cutoff, there were 4 ongoing responses.

The median progression-free survival (PFS) rate was 6.3 months (95% CI, 1.3-11.3), and the 6-month PFS rate was 57.1% (95% CI, 38.8-75.4). Using the reverse Kaplan-Meier method, investigators found that the median follow-up period was 28.5 months.

Subgroup analysis demonstrated that objective tumor responses had no connection with clinical characteristics such as age, race, sex, α-fetoprotein levels, history of prior locoregional therapy, extrahepatic disease, or macrovascular invasion.

The safety analysis reported that 33 (94.3%) patients experienced adverse events (AEs), with 7 (20%) experiencing serious AEs. Grade 3 or higher AEs were reported in 16 (45.7%) patients.

Researchers noted that the trial may have been limited due to the  sample size, lack of blinding in radiographic assessments, and single-arm design. They concluded that further studies should test a randomized setting.

“However, the encouraging results of this study lend support to future investigations testing anti-phosphatidylserine agents in combination with anti–PD-1/L1 therapies or existing frontline immunotherapy regimens,” the investigators wrote.