GNOS-PV02

We present results from a single-arm, open-label, phase 1/2 study of a DNA plasmid PTCV (GNOS-PV02) encoding up to 40 neoantigens coadministered with plasmid-encoded interleukin-12 plus pembrolizumab in patients with advanced HCC previously treated with a multityrosine kinase inhibitor. Our results support the PTCV's mechanism of action based on the induction of antitumor T cells and show that a PTCV plus pembrolizumab has clinical activity in advanced HCC. ClinicalTrials.gov identifier: NCT04251117 .

NeXT Personal®, an ultra-sensitive tumor-informed ctDNA assay was used to longitudinally track ctDNA in advanced hepatocellular carcinoma (HCC) patients treated with GNOS-PV02 (a personalized therapeutic DNA cancer vaccine) in combination with pembrolizumab.Advanced unresectable or metastatic HCC patients that progressed on, or were intolerant to, first-line TKI therapy were enrolled into the Phase 1b/2a GT-30 study [NCT04251117]. ctDNA clearance was observed in all 3 CR patients with a lead time of 483, 126 and 105 days compared with MRI.This ultra-sensitive ctDNA assay shows significant association between ctDNA change and clinical response and survival, and can be used to accurately predict clinical outcome. The convenience of non-invasive liquid biopsy and rapid availability of data could enable the use of ctDNA to allow real-time monitoring of personalized cancer immunotherapy.

P1/2, N=36, Active, not recruiting, Geneos Therapeutics | Recruiting --> Active, not recruiting | Trial completion date: Aug 2023 --> Jun 2025

We used an ultra-sensitive, tumor-informed ctDNA platform to longitudinally track tumor neoantigen targets and monitor molecular residual disease (MRD) in advanced HCC patients (pts) being treated with a DNA personalized therapeutic cancer vaccine (GNOS-PV02). Highly sensitive tracking of MRD and neo-antigenic variants over the course of therapy was achieved using a single assay. We show that ctDNA can sensitively monitor disease status non-invasively, potentially leading to accurate clinical outcome prediction. Additionally, the ease of sample handling, analysis, and rapid availability of data could enable the use of ctDNA monitoring to allow real-time dynamic personalized cancer immunotherapy.

P1/2 | "Trial Registration NCT04251117 Ethics Approval For GT-30 trial, the protocols were approved by Johns Hopkins Medicine Review Boards (CR00039002/IRB00227771), Icahn School of Medicine-Program for the Protection of Human Subjects (20-00076 GCO#1), and Northern A Health and Disability Ethics committee (Ethics ref: 20/NTA), respectively. Written informed consent was obtained from each patient prior to the patient participating in the trial."

P1/2 | "Methods A 74 yo white male, having progressed on multiple prior lines of therapy including ablation, TACE and lenvatinib, was enrolled in the GT-30 study. Trial Registration NCT04251117 Ethics Approval For GT-30 trial, the protocols were approved by Johns Hopkins Medicine Review Boards (CR00039002/IRB00227771), Icahn School of Medicine-Program for the Protection of Human Subjects (20-00076 GCO#1), and Northern A Health and Disability Ethics committee (Ethics ref: 20/NTA), respectively. Written informed consent was obtained from each patient prior to the patient participating in the trial."

P1/2, N=36, Recruiting, Geneos Therapeutics | N=24 --> 36 | Trial completion date: Feb 2022 --> Aug 2023 | Trial primary completion date: Dec 2021 --> Jun 2023

Conclusions These data demonstrate the potential of GNOS-PV02 + INO-9012 with pembrolizumab to target multiple neoepitopes, and provide initial support for the safety and efficacy of this regimen in patients with advanced HCC. Trial Registration NCT04251117

The GT-30 trial (NCT04251117) is a single-arm phase I/II clinical trial to assess the safety, immunogenicity, and preliminary efficacy of GNOS-PV02 in combination with INO-9012 and pembrolizumab in patients with advanced HCC . Clinical activity is assessed by RECIST1.1 at baseline and every 9 weeks . Serial biopsies will be obtained at 9 weeks and upon disease progression to evaluate changes in the exome, transcriptome and changes to the tumor microenvironment.