Novel Vaccine Platform Plus Pembrolizumab May Boost Immune Response in Advanced HCC

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A novel vaccine platform administered in combination with pembrolizumab appears to be safe and effective in patients with advanced hepatocellular carcinoma (HCC), according to data presented by Mark Yarchoan, MD, and colleagues at the Society for Immunotherapy of Cancer (SITC) 2021 Annual Meeting (Abstract 453).

Interim data from the phase I/II clinical trial demonstrated a response rate of 25% in the first 12 patients treated, which compares favorably to available data for PD-1 therapy alone. Responses also appeared to be durable, the study authors reported.  

“These results appear to show that the DNA vaccine is safe and is associated with an encouraging response rate,” said lead study author Dr. Yarchoan, Assistant Professor of Oncology at Johns Hopkins Medicine. “The data also show immunologic changes consistent with response to therapy that was observed.”

Mark Yarchoan, MD

Mark Yarchoan, MD

As Dr. Yarchoan reported, HCC is the fourth most common cause of cancer-related death. Immune checkpoint inhibitors targeting PD-1 have limited activity in HCC as monotherapy, with response rates ranging from 14% to 17%.

“As we now increasingly understand, tumor-specific antigens or neoantigens seem to be the most important antigens for the immune system in augmenting antitumor immunity,” Dr. Yarchoan explained. “Tumor neoantigens derived from tumor-specific mutations can be incorporated into personalized therapeutic cancer vaccines to generate tumor-specific T-cell immunity, potentially priming the immune system for anti–PD-1 therapy.”

GNOS-PV02 and Study Methods

GNOS-PV02, a personalized DNA vaccine, encodes up to 40 patient-specific neoantigens. According to Dr. Yarchoan, preclinical data showed that the novel vaccine platform was able to generate “very robust CD4 and CD8 responses against a range of high-quality neoantigens.”

For this single-arm, phase I/II clinical trial, Dr. Yarchoan and colleagues assessed the safety, immunogenicity, and preliminary efficacy of GNOS-PV02 in combination with plasmid-encoded IL-12 and pembrolizumab, which is already approved in this setting, following first-line treatment with a tyrosine kinase inhibitor.

The investigators enrolled 24 patients with advanced HCC, biopsied their tumors for exome and transcriptome sequencing, and collected peripheral blood for germline sequencing and histogenetics. The tumor-specific vaccine was designed, optimized, and manufactured during first-line therapy.

Response Rate Linked to Immunologic Changes

For this interim analysis, Dr. Yarchoan and colleagues performed a data cut-off on the first 12 patients (median age = 66 years).

The combination of the novel vaccine platform plus plasmid-encoded IL-12 with pembrolizumab led to three partial responses, for a response rate of 25%. An additional five patients (42%) had stable disease, while four patients (33%) had progressive disease.

According to Dr. Yarchoan, these findings compare favorably to the estimated 14% to 17% response rate seen with PD-1 monotherapy.

“The responses also appear to be quite durable,” said Dr. Yarchoan, who noted that one patient with a very large primary lesion in the liver had a “very nice, sustained response.”


  • Results of a phase I/II trial show the potential of novel vaccine platform with pembrolizumab to target multiple neoepitopes.
  • Findings provide initial support for the safety and efficacy of this regimen in patients with advanced HCC.

Analysis of the TCR repertoire in peripheral blood and tumor tissue also identified novel and significantly expanded T-cell clones post-vaccination in all patients analyzed.

“Compared to pretreatment, there are a number of new TCR clones that emerged in the post-treatment blood, which were not present in the blood at baseline,” said Dr. Yarchoan, who noted that many of the novel peripheral T-cell clones were also found to be present within the tumor. “This provides some initial evidence that the therapy is associated with the generation of vaccine-induced TCR clones that traffic to the tumor microenvironment.”

However, according to Dr. Yarchoan, ongoing work is needed to conclusively demonstrate that TCR clones are, in fact, responding to the vaccine.

Investigators noted that the treatment was well tolerated. The most common treatment-related adverse events were grade 1 fatigue (25%) and grade 1 injection site reactions (17%).

The study authors concluded, “These data demonstrate the potential of GNOS-PV02 plus plasmid-encoded IL-12 with pembrolizumab to target multiple neoepitopes, and provide initial support for the safety and efficacy of this regimen in patients with advanced HCC.”

Disclosure: Dr. Yarchoan had no relevant financial disclosures.