Personalized Therapeutic Vaccine Plus Pembrolizumab for Patients With Advanced HCC

A single-arm, phase 1/2 study from Mark Yarchoan, MD, and colleagues sought to determine the efficacy of a personalized neoantigen vaccine plus pembrolizumab for patients with advanced hepatocellular carcinoma (HCC).

The findings were published in Nature Medicine.

Researchers noted that a personalized therapeutic cancer vaccine (PTCV) might increase patient response to PD-1 inhibitors through the induction of tumor-specific immunity.

Thirty-six patients with advanced HCC who previously underwent treatment with a multityrosine kinase inhibitor received a DNA plasmid PTCV encoding up to 40 neoantigens coadministered with plasmid-encoded interleukin-12 plus pembrolizumab.

The primary end points were safety and immunogenicity, while secondary end points were treatment efficacy and feasibility.

In patients with solid tumors (n=11), the objective response rate per Response Evaluation Criteria in Solid Tumors v1.1 was 30.6%, with 3 (8.3%) patients experiencing a complete response. In 19 (86.4%) of the 22 evaluable patients, researchers confirmed neoantigen-specific T-cell responses through enzyme-linked immunosorbent spot assays.

Using multiparametric cellular profiling, investigators found active, proliferative, and cytolytic vaccine-specific CD4+ and CD8+ effector T cells. Vaccination-enriched T-cell clone expansion and tumor infiltration was identified through T-cell receptor (TCR) β-chain bulk sequencing.

Dr. Yarchoan and colleagues noted that reactivity against vaccine-encoded neoantigens was confirmed using TCR complementarity-determining region cloning of expanded T-cell clones in the tumors following vaccination. Post-treatment T-cell clonal expansion of cytotoxic T-cell phenotypes was identified through single-cell analysis.

Investigators concluded that PTCV plus pembrolizumab demonstrates clinical activity in patients with advanced HCC.

“The study provides evidence that a personalized [antitumor] vaccine can enhance clinical responses to anti–PD-1 therapy. A larger randomized clinical trial will be needed to confirm this finding, but the results are incredibly exciting,” said Dr. Yarchoan. “The role of personalized [antitumor] vaccines is expanding.”