GNOS-PV02 / Geneos Therap - LARVOL DELTA

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

Personalized Vaccines Show Promise for Hard-to-Treat Cancers (Cancer Health) - "Mark Yarchoan, MD...presented findings from a Phase I/II trial of a personalized vaccine for hepatocellular carcinoma (HCC), the most common type of primary liver cancer. Often caused by viral hepatitis, fatty liver disease or heavy alcohol use, HCC is typically diagnosed late, and it is one of the leading causes of cancer-related death worldwide."

P1/2 data

Personalized Neoantigen DNA Vaccine (GNOS-PV02) and Pembrolizumab Develop Antitumor Poly-Functional Neoantigen-Specific CD4+ and CD8+ Effector T Cells in Advanced Hepatocellular Carcinoma Therapy (ASGCT 2024) - "Our data shows that the personalized DNA-based vaccine in combination with pembrolizumab generates a significant poly-functional neoantigen-specific antitumor CD8+ and CD4+ T cell responses, including T cell clonal expansion and infiltration to the tumor. These features could explain the mechanism of action behind the clinical activity observed in advanced HCC patients."

IO biomarker • Metastases • Tumor-specific neoantigens • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD4 • CD8 • CXCR6 • IFNG • IL12A • TIGIT • TRB

Cancer vaccine with immunotherapy shrinks liver tumors, trial shows Share on Pinterest (Medical News Today) - "'Essentially GNOS-PV02 aims to (educate) the immune system to recognize antigens that are present in the cancer so that the immune system can better recognize and attack cancer cells,' explained lead study author Mark Yarchoan, MD...'Despite recent advances in the treatment of HCC, only a minority of patients respond to contemporary systemic treatments and the prognosis for patients with advanced disease is inferior to most other tumor types,' Yarchoan said."

Media quote

Personalized neoantigen DNA vaccine GNOS-PV02 and pembrolizumab as second-line treatment for advanced hepatocellular carcinoma (AACR 2024) - "Our results show that a PTCV plus PEMBRO is well tolerated and has clinical activity in pts with advanced HCC, and support the PTCV mechanism of action based on the induction of anti-tumor T cells in peripheral blood and tumor. A confirmatory phase 3 clinical study assessing OS is planned."

Clinical • Metastases • Tumor-specific neoantigens • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD4 • IFNG • IL12A • TRB

Detection of circulating tumor DNA predicts survival in advanced HCC patients treated with personalized therapeutic DNA cancer vaccine in combination with immune checkpoint blockade (AACR 2024) - P1/2 | "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."

Checkpoint block • Checkpoint inhibition • Circulating tumor DNA • Clinical • Combination therapy • Metastases • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • IL12A

Geneos Therapeutics Announces Positive Phase 1/2 Data for GT-30 Trial of Personalized Therapeutic Cancer Vaccine (PRNewswire) - P1/2a | N=36 | NCT04251117 | Sponsor: Geneos Therapeutics | "The study met its primary endpoints of safety and immunogenicity and its secondary endpoint of efficacy based on observed response rate (ORR)....PTCV-related adverse events were all limited to Grades 1 and 2 with no dose-limiting toxicities or grade > 3 adverse events observed. The most common adverse events were injection site reactions observed in 41.6% (15/36) of patients....The ORR for GT-30 is currently at 30.6% (11/36), including three complete responses (CR) and eight partial responses....Today Geneos also presented selected GT-30 clinical trial data and updated longitudinal circulating tumor DNA (ctDNA) biomarker data from the trial at the 2024 American Association for Cancer Research (AACR) Annual Meeting in San Diego. Reductions of at least 50% versus baseline in patient ctDNA, an exploratory endpoint, were seen in 40.7% of patients (11 of 27 patients for whom the full data set are available)."

P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial. (PubMed, Nat Med) - P1/2 | "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 ."

Journal • Metastases • P1/2 data • Tumor-specific neoantigens • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD4 • CD8 • IL12A • TRB

Geneos Therapeutics to Present New Clinical Data on GNOS-PV02 at the 2024 American Association for Cancer Research (AACR) Annual Meeting (PRNewswire) - "Geneos Therapeutics...announced the upcoming presentation of two posters sharing new clinical data from its Phase 1b/2a GT-30 study of GNOS-PV02, a personalized neoantigen DNA vaccine, in patients with advanced hepatocellular carcinoma, at the 2024 American Association for Cancer Research (AACR) Annual Meeting. The AACR Annual Meeting will be held in San Diego from April 5-10."

P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Geneos Therapeutics Closes its Series A3 Financing With Investment of $5 Million (PRNewswire) - "Geneos Therapeutics...announced that it has completed its Series A3 financing round with an additional investment of $5 million, totaling $10 million....Proceeds Will Fund Completion of Phase 1b/2a GT-30 Program; GT-30 is evaluating the safety, and efficacy of PTCV (GNOS-PV02 plus plasmid-encoded IL-12) administered in combination with the immune checkpoint inhibitor pembrolizumab, in 36 patients with unresectable or metastatic hepatocellular carcinoma (HCC) who progress on, or are intolerant to, first-line tyrosine kinase inhibitors (sorafenib or lenvatinib). Study enrollment completed in June of this year with the top-line safety and clinical response data from the complete cohort of 36 patients is anticipated by the end of the year."

Financing • P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Geneos Therapeutics Announces Eight of 34 Patients to Achieve Complete Response, Complete Molecular Response, or, Secondary Resectability in Ongoing Clinical Trial of Personalized Therapeutic Cancer Vaccination in Second Line Advanced Liver Cancer (PRNewswire) - P1b/2a | N=36 | NCT04251117 | Sposnor: Geneos Therapeutics | "Geneos Therapeutics...announced updated data from GT-30, an ongoing single-arm open-label multi-center Phase 1b/2a study in second-line advanced hepatocellular carcinoma (HCC)....Geneos reports today that four additional patients have achieved a complete molecular response (CMR) by ultrasensitive, third-generation, circulating tumor DNA (ctDNA) analysis. The ctDNA dropped below the limit of detection in all four patients. By RECIST1.1, three of these four patients are durable partial responses (PR) and one a durable stable disease (SD). Applying mRECIST criteria as additional evaluation, each of the three PR patients is a CR and the SD patient is a PR."

P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

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

Tracking MRD and neoantigen targets using a tumor-informed liquid biopsy platform in HCC patients treated with personalized cancer vaccine and pembrolizumab. (ASCO 2023) - P1/2 | "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."

Biopsy • Clinical • IO biomarker • Liquid biopsy • Tumor-specific neoantigens • Hepatocellular Cancer • Hepatology • Oncology • IL12A

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

Effect of personalized immunization with GNOS-PV02 of patients with hepatocellular carcinoma on TCR clonal expansion, tumor infiltration, and vaccine-specific reactivity. (ASCO 2023) - P1/2 | " Paired blood and tumor biopsy samples from patient #8 enrolled in the GT-30 study were collected before and after treatment with GNOS-PV02 (1mg) + plasmid-encoded IL-12 (0.3mg) + Pembrolizumab (200mg). PTCV treatment resulted in neoantigen-specific T cell responses, clonal expansion in the periphery and primary lesion, and tumor infiltration of T cells with an activated phenotype. TCR-engineered high-frequency T cells found in the tumor are reactive to PTCV-encoded neoantigens post-treatment. These results may account for the observed objective decrease in the primary tumor size."

Clinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD4 • CD69 • CD8 • IFNG • IL12A • TRB

Immune pressure in an advanced hepatocellular cancer patient following treatment with personalized neoantigen DNA vaccine (GNOS-PV02) in combination with plasmid IL-12 (pIL12) and anti-PD1 (pembrolizumab) (SITC 2022) - 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."

Clinical • Combination therapy • IO biomarker • Tumor-specific neoantigens • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • CD4 • CD69 • CD8 • IFNG • IL12A

Geneos Therapeutics Announces Positive Clinical Data for Personalized Therapeutic Cancer Vaccines in Ongoing Liver Cancer Trial (PRNewswire) - "'While overall cancer rates are decreasing worldwide, HCC deaths are rising in the United States and globally, and the etiology of disease is shifting from viral to non-viral causes. HCC is resistant to immune checkpoint therapies in the majority of patients due to the largely immune excluded tumor microenvironment. Therapies that can bring CD8+ T cells into the tumor microenvironment, such as effective therapeutic cancer vaccines targeting cancer neoantigens, can reprogram the tumor microenvironment for checkpoint inhibitor therapy,' stated Mark Yarchoan..."

Media quote

Circulating tumor DNA analysis of advanced hepatocellular cancer (HCC) patients treated with neoantigen targeted personalized cancer DNA vaccine (GNOS-PV02) in combination with plasmid IL-12 (pIL12) and anti-PD1 (pembrolizumab) (SITC 2022) - 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."

Circulating tumor DNA • Clinical • Combination therapy • IO biomarker • Tumor-specific neoantigens • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • IL12A

Geneos Therapeutics Secures $5 Million in Series A3 Financing (PRNewswire) - "Geneos Therapeutics...announced that it has secured $5 million in its Series A3 round. This financing adds 3B Future Health Fund (3B FHF) to Geneos' investor syndicate....Proceeds Will Fund Expansion of Phase 1b/2a GT-30 Program....Geneos plans to report the efficacy and durability of response data from the full cohort of 36 patients in 2023."

Financing • P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology

Geneos Therapeutics Announces Another Complete Response in Ongoing Clinical Trial of Personalized Therapeutic Cancer Vaccination in Second Line Advanced Liver Cancer (PRNewswire) - P1/2a | N=36 | NCT04251117 | "Geneos Therapeutics...announced that a third patient has achieved a complete response (CR) among the first 24 patients (23 evaluable) enrolled in GT-30, an ongoing single-arm open-label multi-center Phase 1b/2a study. Overall response rate by RECIST 1.1 is 30.4% in the evaluable patients consisting of three complete responses, four partial responses, six stable disease, and ten progressive disease....In addition to the three CRs, a fourth patient is also cancer-free after liver and lung lesions shrank to become fully responsive to surgery and radiation, thereby achieving secondary resectability....Based on the full 24-patient data, which were presented at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting last month, Geneos has expanded GT-30 to enroll a further 12 patients, with first reports on benchmark overall survival (OS) from the full cohort of 36 anticipated in mid-2023."

Enrollment status • P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology

Geneos Therapeutics Announces Positive Clinical Data for Personalized Therapeutic Cancer Vaccines in Ongoing Liver Cancer Trial (PRNewswire) - "Abstract #691 details a case study from GT-30 of a patient whose PTCV, designed based on the neoantigen content of a liver tumor primary lesion, resulted in a clinical PR. Profound shrinkage and control of the liver lesion resulted, now continuing for over a year. A metastatic adrenal lesion newly developed four months post initial treatment, the neoantigen content of which was similar but not identical to the liver primary lesion: while 16 of the original liver neoantigens remain, all four of the vaccine epitopes with strongest T cell responses were absent in the adrenal lesion....Abstract #692 summarizes the use of circulating tumor DNA (ctDNA) analysis in the GT-30 trial, to monitor tumor burden (progression or reduction). It was concluded that ctDNA may be a useful tool for monitoring disease in a patient specific manner."

Clinical data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Geneos Therapeutics Announces Positive Clinical Data for Personalized Therapeutic Cancer Vaccines in Ongoing Liver Cancer Trial (PRNewswire) - P1/2 | N=36 | NCT04251117 | Sponsor: Geneos Therapeutics | "Geneos Therapeutics...announced positive safety and efficacy data from the first 24 patients (23 evaluable) enrolled in GT-30....By RECIST1.1, disease control rate is 54.2 percent (13/24; mITT) consisting of two complete responses (CR), five partial responses (PR), six stable disease (SD) and 10 progressive disease (PD); A third patient (deemed a radiological PR) is cancer-free after a liver primary lesion and two lung metastases all reduced in size to become fully responsive to surgery and radiation therapy...Based on the 24-patient data, Geneos has expanded GT-30 to enroll a further 12 patients, with first reports on benchmark overall survival (OS) from the full cohort of 36 anticipated in mid-2023. In parallel, the company is developing plans for a potential registrational trial in advanced HCC with its medical advisors and preparing for discussion with regulatory agencies."

P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

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

Personalized neoantigen DNA vaccines expand tumor-specific T cells in the periphery which infiltrate the tumor in hepatocellular carcinoma. (ASCO 2022) - "GNOS-PV02, a neoantigen DNA vaccine, in combination with plasmid IL-12 and pembrolizumab resulted in expansion of newly identified T cells, primarily activated CD8, which trafficked to the tumor. These new tumor infiltrating T cells showed TCR specificity against tumor neoantigens encoded in GNOS-PV02 and may account for the observed objective decrease in tumor size."

Tumor-specific neoantigens • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • CD4 • CD69 • CD8 • IL12A