rocakinogene sifuplasmid (INO-9012)

P1/2, N=35, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=9, Active, not recruiting, Washington University School of Medicine | Trial completion date: Dec 2023 --> Dec 2024

P1, N=33, Active, not recruiting, National Cancer Institute (NCI)

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

P1, N=9, Active, not recruiting, Washington University School of Medicine | Trial completion date: Apr 2023 --> Dec 2023

We studied the safety and immunogenicity of a novel therapeutic hepatitis C virus (HCV) genotype 1a/1b consensus DNA vaccine, INO-8000, encoding HCV NS3, NS4A, NS4B, and NS5A proteins alone or co-administered with DNA-encoding IL12 (INO-9012), a human cytokine that stimulates cellular immune function, in individuals with chronic hepatitis C. This was a phase I, multisite dose-escalation trial with an expansion cohort evaluating doses of 0, 0.3, 1.0, and 3.0 mg of INO-9012 (IL12 DNA) as an addition to 6.0 mg of (INO-8000; HCV DNA vaccine). The administration of IL12 DNA along with a hepatitis C viral antigen DNA vaccine enhanced the HCV-specific immune responses induced by the vaccine in individuals with chronic hepatitis C, an important cause of hepatocellular carcinoma. IL12 could be an effective adjuvant in vaccines targeting HCV and other oncogenic viruses.

We studied the safety and immunogenicity of a novel therapeutic hepatitis C virus (HCV) genotype 1a/1b consensus DNA vaccine, INO-8000, encoding HCV NS3, NS4A, NS4B and NS5A proteins alone or co-administered with DNA encoding interleukin-12 (IL-12) (INO-9012), a human cytokine that stimulates cellular immune function, in individuals with chronic hepatitis C. This was a phase I, multi-site dose-escalation trial with an expansion cohort evaluating doses of 0, 0.3, 1.0, and 3.0 mg of INO-9012 (IL-12 DNA) as an addition to 6.0 mg of (INO-8000) (HCV DNA vaccine) . The addition of 1.0 mg of IL-12 DNA provided the best enhancement of immune responses. The vaccine regimen had little effect on controlling HCV viremia.

P1, N=9, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | Trial completion date: Nov 2024 --> Apr 2023 | Trial primary completion date: Dec 2023 --> May 2022

P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

P1, N=12, Recruiting, Washington University School of Medicine | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Dec 2022 --> Dec 2023

P1, N=12, Recruiting, Washington University School of Medicine | Trial completion date: Jul 2023 --> Nov 2023 | Trial primary completion date: Aug 2022 --> Dec 2022

P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Jun 2022 --> Dec 2022 | Trial primary completion date: Jun 2022 --> Dec 2022

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

P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Dec 2021 --> Jun 2022 | Trial primary completion date: Dec 2021 --> Jun 2022

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

P1, N=12, Recruiting, Washington University School of Medicine | Trial completion date: Jul 2024 --> Jul 2023 | Trial primary completion date: Oct 2023 --> Aug 2022

Plasmid DNA-encoded hTERT/IL-12 DNA immunotherapy was well-tolerated, immune responses were noted across all tumor types, and a specific CD8+ phenotype increased by the immunotherapy was significantly correlated with survival in patients with pancreatic cancer.

P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Jun 2021 --> Dec 2021 | Trial primary completion date: Jun 2021 --> Dec 2021

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.

P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Jan 2021 --> Jun 2021 | Trial primary completion date: Jan 2021 --> Jun 2021

P1, N=6, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

P1, N=6, Not yet recruiting, Washington University School of Medicine | Trial completion date: Apr 2024 --> Aug 2024 | Initiation date: Apr 2020 --> Aug 2020 | Trial primary completion date: Jul 2023 --> Nov 2023

Treatment with INO-5150 +/- INO-9012 in PCa patients drove the expansion of a diverse pool of antigen specific T cells with a high Shannon’s Entropy value suggesting high TCR diversity. Patients with immune reactivity by flow cytometry were more likely to have a higher frequency of PSA/PSMA specific TCRs that expanded >10 fold over their pre-treatment value; however patients without immune reactivity also demonstrated expansion in TCRs. These data suggest that INO-5150 induced PSA/PSMA specific T cells and that TCR sequencing is a valuable tool for assessment of immune responses induced by immunotherapy that does not bias towards a specific T cell function.

INO-3106, with INO-9012, given IM followed by EP with CELLECTRA® is tolerable, immunogenic, and may provide clinical benefit. A larger study is currently planned to explore the efficacy of this therapy in adults, adolescents and children with RRP.

INO-5150 is a synthetic DNA therapy that includes plasmids encoding for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA), and INO-9012 is a synthetic DNA plasmid encoding for interleukin-12 (IL-12). Immunogenicity was observed in 76% (47/62) of patients by multiple assessments. Analysis indicated that CD38 and perforin co-positive CD8 T cell frequency correlated with attenuated PSA rise (p = 0.05, n = 50).

P1, N=6, Not yet recruiting, Washington University School of Medicine | Trial completion date: Dec 2023 --> Mar 2024 | Initiation date: Dec 2019 --> Mar 2020 | Trial primary completion date: Mar 2023 --> Jun 2023

In this phase 1 dose-escalation study, synthetic optimized DNA plasmids that target hTERT (INO-1400, or mutant hTERT; and INO-1401, or SynCon® TERT) were delivered intramuscularly followed by EP with the CELLECTRA® device, to assess safety, tolerability and immune effects of immunotherapy with INO- 1400 or INO-1401, alone or co-administered with a plasma encoding for human IL-12 (INO-9012) in adult patients with cancer. Conclusions INO-1400/01 with or without INO-9012 given IM with EP is well-tolerated in adults with solid tumors, and can generate active hTERT-specific T cells, suggesting an ability to break immune tolerance. Dosing is complete, and follow-up is ongoing.