ProstVac (rilimogene galvacirepvec) / National Cancer Institute, Bavarian Nordic - LARVOL DELTA

Combination Immunotherapy in Biochemically Recurrent Prostate Cancer (clinicaltrials.gov) - P2 | N=40 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: Jan 2025 ➔ Jun 2024 | Trial primary completion date: Jan 2025 ➔ Jun 2024

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

AIRSTREAM: Artificial Intelligence (AI)-Based Lesion Kinetics Appraisal for the Selection of Therapeutic Targets for Focal Stereotactic Body Radiation Therapy (SBRT) in Patients with Oligoprogressive Metastatic Castration Resistant (mCRPC). (PCF 2024) - P2 | " A previous study (clincialtrials.gov: NCT01867333) conducted at the NCI enrolled patients with mCRPC and treated them with an enzalutamide-based regimen (i.e., enzalutamide with or without a therapeutic cancer vaccine, Prostvac). Utilizing AI-based targeted MDT with SBRT has the potential to prolong the durability of 1st-line standard therapy for patients with advanced prostate cancer. A planned study will prospectively evaluate the use of this AI-based MDT strategy in patients with mCRPC on 1st-line therapy utilizing serial PSMA-based imaging. ."

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

16-C-0048: Docetaxel and PROSTVAC for Metastatic Castration-Sensitive Prostate Cancer (clinicaltrials.gov) - P2 | N=74 | Completed | Sponsor: National Cancer Institute (NCI) | Trial completion date: Aug 2024 ➔ Dec 2023 | Active, not recruiting ➔ Completed

Metastases • Trial completion • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • CEACAM5 • IFNG • IL2 • LAMP1 • TNFA

Combination Immunotherapy in Biochemically Recurrent Prostate Cancer (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=29 ➔ 40

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

PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer (clinicaltrials.gov) - P1/2 | N=24 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4

Adjuvant PROSTVAC-V/F in Subjects at High Risk for Relapse After Radical Prostatectomy (clinicaltrials.gov) - P2 | N=33 | Completed | Sponsor: Medical University of South Carolina | Active, not recruiting ➔ Completed

Trial completion • Oncology • Prostate Cancer

Combination Immunotherapy in Biochemically Recurrent Prostate Cancer (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jan 2024 ➔ Jan 2025 | Trial primary completion date: Jan 2024 ➔ Jan 2025

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

Adjuvant PROSTVAC-V/F in Subjects at High Risk for Relapse After Radical Prostatectomy (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Medical University of South Carolina | Trial completion date: Mar 2024 ➔ Jun 2024 | Trial primary completion date: Dec 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Oncology • Prostate Cancer

Nonsurgical Interventions to Prevent Disease Progression in Prostate Cancer Patients on Active Surveillance: A Systematic Review and Meta-analysis. (PubMed, Eur Urol Oncol) - "The use of 5-ARIs in PCa patients on AS is associated with longer PFS. However, for the other interventions, it is difficult to draw clear conclusions based on the weak available evidence."

Journal • Retrospective data • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Nivolumab increased vaccine induced T-cell infiltration in Prostate cancer (SITC 2023) - P2 | "2 To switch the tumor immune microenvironment phenotype from cold to inflamed we used Prostvac, a therapeutic cancer vaccine that targets prostate-specific antigen (PSA) in monotherapy and in combination with Nivolumab, a PD1 inhibitor. Conclusions Immunotherapy is standard therapy for many tumors, however PD-1 inhibitors as single agents have no clinical role in prostate cancer outside MSI high cancer. Combination immunotherapies could change the tumor immune-microenvironment landscape and enhance immune response by increasing T-cells activation and infiltration and therefore overcoming tumor immune evasion."

IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • FOXP3 • PD-L1

16-C-0048: Docetaxel and PROSTVAC for Metastatic Castration-Sensitive Prostate Cancer (clinicaltrials.gov) - P2 | N=74 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Completed ➔ Active, not recruiting | Trial completion date: Jul 2022 ➔ Aug 2024

Enrollment closed • Metastases • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • CEACAM5 • IFNG • IL2 • LAMP1 • MUC1 • TNFA

Quantitative Analysis of Serial Positron Emission Tomography Imaging in Men with Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide. (PubMed, Eur Urol Oncol) - "These data highlight the dynamic nature of NaF PET in mCRPC patients treated with enzalutamide, where not all new findings were ultimately related to disease progression. This analysis also provides a potential strategy to identify and intervene in oligoprogression in prostate cancer."

Journal • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Adjuvant PROSTVAC-V/F in Subjects at High Risk for Relapse After Radical Prostatectomy (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Medical University of South Carolina | Trial completion date: Sep 2023 ➔ Mar 2024 | Trial primary completion date: Sep 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Oncology • Prostate Cancer

PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer (clinicaltrials.gov) - P1/2 | N=20 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial primary completion date: Nov 2023 ➔ Jun 2023

Combination therapy • IO biomarker • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CTCs • PD-L1

PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer (clinicaltrials.gov) - P1/2 | N=20 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting | N=29 ➔ 20

Combination therapy • Enrollment change • Enrollment closed • IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CTCs • PD-L1

16-C-0048: Docetaxel and PROSTVAC for Metastatic Castration-Sensitive Prostate Cancer (clinicaltrials.gov) - P2 | N=74 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed

Trial completion • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • CEACAM5 • IFNG • IL2 • LAMP1 • MUC1 • TNFA

Combination Immunotherapy in Biochemically Recurrent Prostate Cancer (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

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

Effects of docetaxel on circulating immune cell subsets and association with outcomes in metastatic castration-sensitive prostate cancer. (ASCO-GU 2023) - P2 | " A clinical trial in mCSPC evaluated sequencing docetaxel and ADT with Prostvac, a poxviral vaccine targeting prostate-specific antigen (PSA). This is the first study to demonstrate increases in activated NK cells with lytic and cytokine producing potential after treatment with docetaxel. Given that NK cells are associated with clinical outcomes in prostate cancer (Zhao SG, JNCI, 2019) and that increased NK cells were seen after treatment with enzalutamide as well (Madan, JITC, 2021), developing immunotherapy combinations to capitalize on NK cell activity may be a path forward for developing immunotherapy in prostate cancer. Clinical trial information: NCT02649855."

Immune cell • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • ITGA4

A pilot trial of neoantigen DNA vaccine in combination with nivolumab/ipilimumab and prostvac in metastatic hormone-sensitive prostate cancer (mHSPC). (ASCO 2022) - P1 | "Eligible patients had histologically confirmed high risk mHSPC, must have completed a course of docetaxel and received continuous androgen deprivation therapy. This is the first clinical trial evaluating the use of personalized neoantigen vaccines in a combination immunotherapeutic approach in mHSPC patients."

Combination therapy • IO biomarker • Tumor-specific neoantigens • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Prostate Cancer • Solid Tumor • TMB

Immune changes after enzalutamide (Enza) is added to androgen-deprivation therapy (ADT) in first-line metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2022) - P2 | "Methods Pts with mCRPC who had progression on ADT alone were randomized to either enza or enza+prostvac(P), a therapeutic cancer vaccine targeting PSA. This compares to enza in BCR without ADT where NK were also increased, but MDSC were decreased, and IL-8 was unchanged. NK which have been associated with better outcomes in prostate cancer are increased after enza in mCRPC and these findings could inform future immunotherapy strategies."

Clinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • CXCL8

Clinical and immunologic impact of short-course enzalutamide alone and with immunotherapy in non-metastatic castration sensitive prostate cancer. (PubMed, J Immunother Cancer) - P2 | "Three months of enzalutamide without ADT induced substantial PSA control beyond the treatment period and was repeatable, perhaps representing an alternative to intermittent ADT in nmCSPC. In addition, enzalutamide was associated with immune changes that could be relevant as future immune combinations are developed. TRAIL REGISTRATION NUMBER: clinicaltrials.gov (NCT01875250)."

Clinical • Journal • Fatigue • Genito-urinary Cancer • Immunology • Oncology • Pain • Prostate Cancer • Solid Tumor

Flutamide With or Without PROSTVAC in Non-metastatic Castration Resistant (M0) Prostate Cancer. (PubMed, Oncologist) - P2 | "The combination of flutamide+PROSTVAC did not improve outcomes in men with nmCRPC compared with flutamide alone. (ClinicalTrials.gov Identifier: NCT00450463)."

Clinical • Journal • Metastases • Genito-urinary Cancer • Immune Modulation • Oncology • Prostate Cancer • Solid Tumor

Adjuvant PROSTVAC-V/F in Subjects at High Risk for Relapse After Radical Prostatectomy (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Medical University of South Carolina | Trial completion date: Jun 2023 ➔ Sep 2023 | Trial primary completion date: Mar 2023 ➔ Jun 2023

Trial completion date • Trial primary completion date • Oncology • Prostate Cancer

Surgical Outcomes in Patients Receiving Neoadjuvant Vaccine Therapy (PROSTVAC) Prior to Radical Prostatectomy: A Phase II Experience (AUA 2023) - P2 | "PROSTVAC was well tolerated and demonstrated the feasibility of neoadjuvant vaccination strategies for localized PCa. Further studies will be needed to elucidate the effectiveness of this vaccine therapy on short and long-term oncologic outcomes."

Clinical • P2 data • Cardiovascular • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

[VIRTUAL] Clinical and immune responses to immunotherapy in biochemically recurrent (non-metastatic castration sensitive) prostate cancer (BCRpc) (ESMO 2020) - P2 | "Background PROSTVAC (P) is a therapeutic cancer vaccine targeting PSA...Funding: Bavarian Nordic. Clinical trial identification: NCT02649439."

Clinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTLA4 • NKG2D • PD-1 • PD-L1