MVI-816 / Madison Vaccines - LARVOL DELTA

Prostate tumor immune microenvironment changes following immunotherapy shared by patients who developed anti-tumor response or immune-related adverse events. (PubMed, Oncoimmunology) - P1/2 | "We previously reported a clinical trial (NCT02499835) evaluating PD-1 blockade combined with an anti-tumor DNA vaccine, pTVG-HP (encoding prostatic acid phosphatase), in patients with metastatic castration-resistant prostate cancer...These findings suggest that patients experiencing irAEs can have immune responses to tumor irrespective of obvious anti-tumor efficacy, at least with these treatments, and underscore the importance of tumor-infiltrating professional antigen presenting cells and T-cell activation for successful immunotherapy. Moreover, our findings suggest that combining vaccines and PD-1 blockade with MDSC-targeting therapies, anti-VISTA, and/or anti-PARP therapies might be further explored."

Adverse events • IO biomarker • Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ACPP • PARP1 • PSAP • VSIR

Trial of pTVG-HP+Nivo+Targeted Ablation of Resistant Lesions in Non-Castrate RecurrentOMPC (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: University of Wisconsin, Madison | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase 2 trial of pTVG-HP DNA vaccine, with or without pTVG-AR DNA vaccine, and pembrolizumab in patients with castration-resistant, metastatic prostate cancer (SITC 2025) - "Vaccines were provided by Madison Vaccines, Inc. Additional funding support was provided by the Prostate Cancer Foundation.Trial Registration Trial Registration: NCT04090528Ethics Approval This study was approved by the University of Wisconsin Health Sciences IRB, approval number 2018-0938."

Clinical • Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ACPP • PSAP

Trial of pTVG-HP+Nivo+Targeted Ablation of Resistant Lesions in Non-Castrate RecurrentOMPC (clinicaltrials.gov) - P1 | N=14 | Not yet recruiting | Sponsor: University of Wisconsin, Madison

New P1 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Spatial proteomic analysis reveals vaccine and PD-1 blockade elicits changes to the prostate tumor immune microenvironment with infiltration of dendritic cells and activated CD8 T cells (IMMUNOLOGY 2025) - P1/2 | "In 66 patients with metastatic, castration-resistant prostate cancer, we reported that concurrent, but not sequential, treatment with DNA vaccine encoding prostatic acid phosphatase (pTVG-HP) and PD-1 blockade resulted in PSA declines in 35% (>50% declines in 10%) patients, reductions in tumor volumes, and 47.2% six-month progression free survival (PFS) rate [NCT02499835]...Increased PARP expression in non-responders and in patients w/o irAEs suggested a potential resistance mechanism. These findings emphasize the role of tumor-infiltrating antigen presenting cells and T cell activation in therapeutic response to vaccine + PD-1 blockade and suggest that further combination with PARP inhibition or treatments targeting MDSC might increase treatment efficacy.Keywords: Animals Human; Cells Dendritic Cells T Cells; Processes Antigen Presentation/Processing Cell Activation"

IO biomarker • Omic analysis • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ACPP • PSAP

Toll like receptor agonists can affect the activation of human CD8+ T cells with downregulation of T cell checkpoint receptor expression (SITC 2024) - "PBMCs from HLA-A2+ patients previously treated with a tetanus vaccine and an antitumor DNA vaccine (pTVG-HP, encoding prostatic acid phosphatase, PAP) were stimulated with tetanus toxoid or PAP-derived HLA-A2 peptide epitopes (TLMSAMTNL, ALDVYNGLL) for 72 hours in the presence of TLR agonists, and culture supernatant was evaluated for the presence of IFNγ by ELISA...Conclusions TLR agonists can support vaccine-mediated activation of human CD8+ T cells and modulate the expression of T cell checkpoint receptors, including CTLA-4. These data provide the rationale for choosing the optimal TLR agonists to improve the efficacy of human anti-cancer vaccines."

IO biomarker • Oncology • ACPP • CD8 • IFNG • IL12A • LAG3 • PD-1 • PSAP • TIGIT • TLR3 • TLR7 • TLR8

Long-term follow up of patients treated with a DNA vaccine (pTVG-HP) for PSA-recurrent prostate cancer (ESMO 2024) - P1, P2 | "Immunization with pTVG-HP was not associated with late adverse events years after administration. The detection of immune responses to the vaccine target years after immunization suggests durable immunity can be elicited in some patients using a DNA vaccine encoding a tumor-associated antigen."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ACPP • CSF2 • PSAP

Long-term follow up of patients treated with a DNA vaccine (pTVG-hp) for PSA-recurrent prostate cancer. (PubMed, Hum Vaccin Immunother) - P1, P2 | "The presence of T-cells specific for the PAP target antigen was detectable in 6/10 (60%) individuals with nmCSPC, and 3/5 (60%) individuals with nmCRPC, many years after immunization. The detection of immune responses to the vaccine target years after immunization suggests durable immunity can be elicited in patients using a DNA vaccine encoding a tumor-associated antigen.Trial Registration: NCT00582140 and NCT00849121."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ACPP • CSF2 • PSAP

NCI-2018-01474: pTVG-HP and Nivolumab in Patients With Non-Metastatic PSA-Recurrent Prostate Cancer (clinicaltrials.gov) - P2 | N=19 | Active, not recruiting | Sponsor: University of Wisconsin, Madison | Trial completion date: Nov 2024 ➔ Dec 2027

Metastases • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

NCI-2019-07273: pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer (clinicaltrials.gov) - P2 | N=61 | Active, not recruiting | Sponsor: University of Wisconsin, Madison | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

NCI-2019-07273: pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: University of Wisconsin, Madison | Trial completion date: Dec 2025 ➔ Oct 2026 | Trial primary completion date: Mar 2024 ➔ Jan 2025

Metastases • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase 2 trial of a DNA vaccine (pTVG-HP) and nivolumab in patients with castration-sensitive non-metastatic (M0) prostate cancer. (PubMed, J Immunother Cancer) - P2 | "In this population, combining nivolumab with pTVG-HP vaccination was safe, and immunologically active, prolonged the time to disease progression, but did not eradicate disease. Quantitative imaging suggested that additional treatments targeting mechanisms of resistance may be required to eliminate tumors."

Journal • Metastases • P2 data • Castration-Resistant Prostate Cancer • Endocrine Disorders • Fatigue • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Nephrology • Oncology • Prostate Cancer • Renal Disease • Solid Tumor • ACPP • CXCL9 • PSAP

Phase 2 trial of a DNA vaccine (pTVG-HP) and nivolumab in patients with castration-sensitive non-metastatic (M0) prostate cancer (J Immunother Cancer) - P2 | N=19 | NCT03600350 | "19 patients were enrolled. No patients met the primary endpoint of complete PSA response; however, 4/19 (21%) patients had a PSA decline >50%. Median PSA doubling times were 5.9 months pretreatment, 25.6 months on-treatment (p=0.001), and 9.0 months in the subsequent year off-treatment. The overall median radiographic progression-free survival was not reached. Grade 3 or 4 events included adrenal insufficiency, fatigue, lymphopenia, and increased amylase/lipase. 9/19 (47%) patients developed immune-related adverse effects (irAE)....In this population, combining nivolumab with pTVG-HP vaccination was safe, and immunologically active, prolonged the time to disease progression, but did not eradicate disease."

P2 data • Prostate Cancer

NCI-2018-01474: pTVG-HP and Nivolumab in Patients With Non-Metastatic PSA-Recurrent Prostate Cancer (clinicaltrials.gov) - P2 | N=19 | Active, not recruiting | Sponsor: University of Wisconsin, Madison | Trial completion date: Nov 2023 ➔ Nov 2024

Metastases • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

NCI-2019-07273: pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: University of Wisconsin, Madison | Trial primary completion date: Dec 2023 ➔ Mar 2024

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Review of Clinical Trials of Cancer and Its Treatment as a Vaccine. (PubMed, Rev Recent Clin Trials) - "This brief discussion of vaccines and their varieties with examples also discusses vaccine clinical trials in relation to cancer diseases in this DNA and RNA-based cancer vaccine that has had successful clinical trials like the cervical cancer drug VGX-3100, the kidney cancer drug Pembrolizumab, MGN-1601, the prostate cancer drug pTVG-HP with rhGM-CSF, the melanoma cancer drug proteasome siRNA, and the lung cancer drug FRAME-001."

Journal • Review • Bladder Cancer • Cervical Cancer • Genito-urinary Cancer • Infectious Disease • Kidney Cancer • Lung Cancer • Melanoma • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer (clinicaltrials.gov) - P1/2 | N=66 | Completed | Sponsor: University of Wisconsin, Madison | Active, not recruiting ➔ Completed

IO biomarker • Metastases • Trial completion • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PD-1 • PD-L1

NCI-2018-01474: pTVG-HP and Nivolumab in Patients With Non-Metastatic PSA-Recurrent Prostate Cancer (clinicaltrials.gov) - P2 | N=19 | Active, not recruiting | Sponsor: University of Wisconsin, Madison | Trial completion date: Jan 2025 ➔ Nov 2023 | Trial primary completion date: Jan 2024 ➔ Dec 2022

Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CSF2

Phase 2 trial of a DNA vaccine with pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC) (SITC 2021) - P1/2 | "Background We previously reported a pilot clinical trial using a DNA vaccine encoding prostatic acid phosphatase (pTVG-HP), given over 12 weeks either concurrently or in sequence with pembrolizumab, in patients with mCRPC. This study suggests this approach should be further evaluated in randomized clinical trials for patients with advanced mCRPC. Trial Registration NCT02499835"

Clinical • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ACPP • CD8 • GZMB • IFNG • PSAP

Phase 2 trial of a DNA vaccine with pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC) (SITC 2021) - P1/2 | "Trial Registration NCT02499835 Background We previously reported a pilot clinical trial using a DNA vaccine encoding prostatic acid phosphatase (pTVG-HP), given over 12 weeks either concurrently or in sequence with pembrolizumab, in patients with mCRPC. The association of progression or survival with increased IFNγ, irAE, and vaccine schedule suggests T cell activation by vaccination is critical to the mechanism of action of this combination. This study suggests this approach should be further evaluated in randomized clinical trials for patients with advanced mCRPC."

Clinical • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ACPP • CD8 • GZMB • IFNG • PSAP

Phase II trial of a DNA vaccine with nivolumab in patients with PSA-recurrent, castration-sensitive prostate cancer (nmCSPC) (ESMO 2022) - P2 | "Background We previously reported a trial of a DNA vaccine encoding prostatic acid phosphatase (PAP, pTVG-HP) with pembrolizumab in patients with metastatic, castration-resistant prostate cancer. The absence of complete PSA responses, and the finding that PSA rise recurred after treatment, suggest that either longer therapy, or additional treatments, are required to optimize response. Ongoing and planned trials are assessing vaccines encoding multiple target antigens and/or using combined T-cell checkpoint blockade."

Clinical • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ACPP • GZMB • IFNG • PSAP

Phase 2 trial of T-cell activation using MVI-816 and pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC). (PubMed, J Immunother Cancer) - P1/2 | "Findings here demonstrate that combining programmed cell death 1 blockade with MVI-816 is safe, can augment tumor-specific T cells, and can result in a favorable 6-month disease control rate. Correlative studies suggest T-cell activation by vaccination is critical to the mechanism of action of this combination. Future randomized clinical trials are needed to validate these findings."

Clinical • Journal • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ACPP • CD8 • GZMB • HRD • IFNG • MSI • PD-1 • PSAP

NCI-2018-01474: pTVG-HP and Nivolumab in Patients With Non-Metastatic PSA-Recurrent Prostate Cancer (clinicaltrials.gov) - P2 | N=19 | Active, not recruiting | Sponsor: University of Wisconsin, Madison | Trial completion date: Oct 2023 ➔ Jan 2025 | Trial primary completion date: Oct 2022 ➔ Jan 2024

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CSF2

pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: University of Wisconsin, Madison | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

pTVG-HP and Nivolumab in Patients With Non-Metastatic PSA-Recurrent Prostate Cancer (clinicaltrials.gov) - P2; N=41; Recruiting; Sponsor: University of Wisconsin, Madison; Trial completion date: Oct 2022 ➔ Oct 2023; Trial primary completion date: Oct 2020 ➔ Oct 2022

Clinical • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CSF2