rocakinogene sifuplasmid (INO-9012) / Inovio - LARVOL DELTA

Phase Ib study of a plasmid DNA–based immunotherapy encoding the hTERT, PSMA, and WT1 (INO-5401) +/- IL12 (INO-9012) followed by electroporation in cancer patients and healthy individuals with BRCA1/2 mutations. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT04367675 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • IO biomarker • P1 data • Oncology • BRCA1 • BRCA2 • IL12A • WT1

DNA Vaccine Therapy in Treating Patients With Chronic Hepatitis C Virus Infection (clinicaltrials.gov) - P1 | N=33 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Hepatitis C • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Oncology • Solid Tumor • CD4 • CD8 • IFNG

GT-30: GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects with Advanced HCC (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: Geneos Therapeutics | Completed ➔ Active, not recruiting | Trial completion date: Nov 2024 ➔ Nov 2028

Enrollment closed • Trial completion date • Hepatocellular Cancer • Oncology • Solid Tumor • IFNG

GT-30: GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects with Advanced HCC (clinicaltrials.gov) - P1/2 | N=36 | Completed | Sponsor: Geneos Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Jun 2025 ➔ Nov 2024 | Trial primary completion date: Aug 2023 ➔ Nov 2024

Trial completion • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor • IFNG

Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1 • IDH2 • MGMT

INO-5401 + INO-9012 in Combination With Atezolizumab in Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma (clinicaltrials.gov) - P1/2 | N=35 | Active, not recruiting | Sponsor: Inovio Pharmaceuticals | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Urothelial Cancer

INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov) - P1/2 | N=52 | Active, not recruiting | Sponsor: Inovio Pharmaceuticals | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Combination therapy • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

INO 5401 Vaccination in BRCA1/2 Mutation Carriers (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: University of Pennsylvania | Phase classification: P1b ➔ P1

Phase classification • Oncology • BRCA1 • BRCA2

INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov) - P1/2 | N=52 | Active, not recruiting | Sponsor: Inovio Pharmaceuticals | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Combination therapy • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

INO-5401 + INO-9012 in Combination With Atezolizumab in Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma (clinicaltrials.gov) - P1/2 | N=35 | Active, not recruiting | Sponsor: Inovio Pharmaceuticals | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Urothelial Cancer

Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1 • IDH2 • MGMT

DNA Vaccine Therapy in Treating Patients With Chronic Hepatitis C Virus Infection (clinicaltrials.gov) - P1 | N=33 | Active, not recruiting | Sponsor: National Cancer Institute (NCI)

Trial completion date • Hepatitis C • Hepatology • Infectious Disease • Inflammation • CD4 • CD8 • IFNG

GT-30: GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects With Advanced HCC (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: Geneos Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2023 ➔ Jun 2025

Combination therapy • Enrollment closed • Metastases • Trial completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Personalized DNA neoantigen vaccine (GNOS-PV02) in combination with plasmid IL-12 and pembrolizumab as second-line (2L) treatment for advanced hepatocellular carcinoma (HCC) (SITC 2022) - P1/2 | "Methods Patients with unresectable or metastatic HCC and progression or intolerance on first-line therapy with tyrosine kinase inhibitors (sorafenib or lenvatinib) are enrolled...Conclusions GNOS-PV02 + INO-9012 combined with pembrolizumab in the 2L setting was well tolerated and induced tumor-neoantigen-directed CD8+ T cells and TILs...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."

Clinical • Combination therapy • IO biomarker • Tumor-specific neoantigens • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • IL12A • TMB

Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Apr 2023 ➔ Dec 2023

Trial completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD8 • IDH1 • IDH2 • MGMT

INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12) immunotherapy in biochemically relapsed prostate cancer (ESMO-IO 2017) - P1; "Data demonstrated both PSA and PSMA are immunogenic and INO-5150 induced cellular immune responses. Additional analyses and follow-up are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit that has been initially observed."

Adverse events • Clinical • Prostate Cancer

Synthetic DNA Immunotherapy in Biochemically Relapsed Prostate Cancer (ESMO 2018) - P1; "INO-5150 +/- INO-9012 was safe, well tolerated and immunogenic. Clinical efficacy was observed in the patients with D0 PSADT≤ 12 mos as evidenced by a significant dampening of log2PSA change over time and increased PSADT up to 72 weeks FU. Additional genomic analyses are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit."

Prostate Cancer

Safety and immunogenicity of a DNA-vaccine immunotherapy in men with biochemically (PSA) relapsed prostate cancer (ESMO 2017) - P1; "INO-5150 +/- INO-9012 was safe at dosages examined. Data demonstrated both PSA and PSMA are immunogenic and INO-5150 induced cellular immune responses. Higher proportion of arm A pts showed immunological responses as well as improvements in PSA DT, specifically pts with DT ≤ 12 mos suggesting correlation of immunological efficacy and clinical benefit."

Adverse events • Clinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

Phase I Trial of a Therapeutic DNA Vaccine for Preventing Hepatocellular Carcinoma from Chronic Hepatitis C Virus (HCV) Infection. (PubMed, Cancer Prev Res (Phila)) - "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."

Journal • P1 data • Fibrosis • Gastrointestinal Cancer • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL12A

Phase I Trial of a Therapeutic DNA Vaccine for Preventing Hepatocellular Carcinoma from Chronic Hepatitis C Virus (HCV) Infection. (PubMed, Cancer Prev Res (Phila)) - "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."

Journal • P1 data • Fibrosis • Gastrointestinal Cancer • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL12A

Personalized DNA neoantigen vaccine (GNOS-PV02) in combination with plasmid IL-12 and pembrolizumab for the treatment of patients with advanced hepatocellular carcinoma (SITC 2021) - P1/2 | "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"

Clinical • Combination therapy • IO biomarker • Tumor-specific neoantigens • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD4 • CD8 • IL12A

[VIRTUAL] INO-5401 and INO-9012 delivered intramuscularly (IM) with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma (SNO 2020) - P1/2 | "INO-5401 + INO-9012, a novel DNA plasmid immunotherapy, demonstrates acceptable risk/benefit and generates robust systemic immune responses to encoded tumor antigens when administered with cemiplimab and RT/TMZ in newly diagnosed GBM patients. Overall survival is encouraging. Clinical trial information: NCT03491683."

Combination therapy • IO biomarker • Late-breaking abstract • Glioblastoma • Immune Modulation • Inflammation • Oncology • Solid Tumor • CD8 • IFNG • IL12A

A clinical trial for the safety and immunogenicity of a DNA-based immunotherapy in men with biochemically (PSA) relapsed prostate cancer. (ASCO-GU 2017) - P1; "Background: Introducing amino acid sequence changes in highly expressed self-antigens for androgen sensitive prostate cancer pts might be sufficient to break tolerance, thus a DNA vaccine was developed using SynCon PSA and PSMA (INO-5150) that share 96.8 and 91.6% sequence identities to these native antigens, respectively. INO-5150 (+) or (-) INO-9012 is generally safe and well-tolerable at all 4 dose levels in a biochemically relapsed prostate cancer patient population."

Adverse events • Clinical • Pain • Prostate Cancer

Intramuscular (IM) INO-5401 + INO-9012 with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma. (ASCO 2022) - P1/2 | "INO-5401 + INO-9012 has an acceptable risk/benefit profile and elicits robust immune responses that correlate with enhanced survival when administered with cemiplimab and RT/TMZ to newly diagnosed GBM patients. Pre-treatment gene expression signatures in MGMT-unmethylated patients were statistically associated with OS18. Overall, INO-5401 elicits antigen-specific T cells that can infiltrate GBM tumors."

Combination therapy • IO biomarker • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CD4 • CD69 • CD8 • GZMA • IFNG • IL12A • MGMT • WT1

A clinical trial for the safety and immunogenicity of a DNA-based immunotherapy in men with biochemically (PSA) relapsed prostate cancer. (ASCO 2017) - P1; "We evaluated a DNA vaccine (INO-5150) including SynCon PSA and PSMA. INO-5150 (+) and (-) INO-9012 was generally safe and well-tolerated at all 4 dose levels in this patient population. Preliminary data suggest PSA stabilization in some patients. Immune analyses are ongoing."

Adverse events • Clinical • Biosimilar • Pain • Prostate Cancer