The purpose of this arm of the study is to evaluate the safety of PV-001-DC (autologous monocyte-derived dendritic cells pulsed with tumor lysate) when given in combination with PV-001-DV (Dengue Virus-1 strain #45AZ5) at the dose levels that were identified in the prior 2 arms and to determine if the combination can treat advanced melanoma.
Patients will have a prescribed amount of PV-001-DV injected into one of their melanoma tumors. Patients will go to the clinic and have a needle placed in a vein. The PV-001-DC product will be infused into the patient's vein. Approximately every 3 weeks, for a total of 4 treatments, patients will receive additional infusions of PV-001-DC Patients will be at the clinic for at least 1 hour following the end of each PV-001-DC infusion and if they feel fine, they may go home.
Approximately 49 days after the first infusion, patients will have a scan to see if their tumors have changed in size. Other scans may be performed during the study at different times. Patients will also have their blood and small samples of tumors tested for changes to the immune system. After 365 days, the trial will be completed for that patient.

开始日期2024-04-01

申办/合作机构

Primevax Immuno-Oncology, Inc.初创企业

[+1]

NCT03989895 / Not yet recruiting临床1期

A Study to Evaluate the Safety and Efficacy of PV-001-DV in Combination With Infusion of PV-001-DC in Patients With Advanced Melanoma

The purpose of this arm of the study is to find the best way to give patients this investigational product and determine if it can treat advanced melanoma by stimulating the immune system. PV-001-DV is an attenuated (weakened) strain of dengue virus developed as a potential preventative vaccine for dengue fever by the US Army as Dengue Virus-1 #45AZ5. This is the first time PV-001-DV will be given to patients with melanoma. Up to 4 dose levels of PV-001-DV will tested in this arm. PV-001-DV (at the lowest dose) will be given to a group of 3 people. As each dose level is found to be safe, it will be given to another other 3 people at the next higher dose level, for a total of up to 10 people in this study. Investigators will monitor patients carefully for any harmful side effects. The side effects in people cannot be completely known ahead of time.
Patients must be progressing after having completed prior therapy with a PD-1 / PD-L1 antagonist alone or in combination with anti-CTLA-4. If the patient is positive for BRAF, the patient must have progressed on at least one BRAF inhibitor in addition to a PD-1 / PD-L1 inhibitor alone or in combination with CTLA-4 for metastatic melanoma.
Patients will have a prescribed amount of PV-001-DV injected into one of their melanoma tumors. Scans will be performed during the study at different times to see if their tumors have changed in size. Patients will also have their blood and small samples of tumors tested for changes to the immune system. After 365 days, the trial will be completed for that patient.

开始日期2024-04-01

申办/合作机构

Primevax Immuno-Oncology, Inc.初创企业

[+1]

100 项与 PV001 相关的临床结果

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100 项与 PV001 相关的转化医学

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100 项与 PV001 相关的专利（医药）

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项与 PV001 相关的文献（医药）

2023-07-19·Journal of translational medicine

Attenuated Dengue virus PV001-DV induces oncolytic tumor cell death and potent immune responses.

Article

作者: Gupta, Kajal ; Zloza, Andrew ; Lyday, Bruce ; Singh, Geeta ; Goldufsky, Josef W ; Kaufman, Howard L ; Chen, Tony ; Daniels, Preston ; Marzo, Amanda L ; Williams, Michael D

BACKGROUND:

Viral therapies developed for cancer treatment have classically prioritized direct oncolytic effects over their immune activating properties. However, recent clinical insights have challenged this longstanding prioritization and have shifted the focus to more immune-based mechanisms. Through the potential utilization of novel, inherently immune-stimulating, oncotropic viruses there is a therapeutic opportunity to improve anti-tumor outcomes through virus-mediated immune activation. PV001-DV is an attenuated strain of Dengue virus (DEN-1 #45AZ5) with a favorable clinical safety profile that also maintains the potent immune stimulatory properties characterstic of Dengue virus infection.

METHODS:

In this study, we utilized in vitro tumor killing and immune multiplex assays to examine the anti-tumor effects of PV001-DV as a potential novel cancer immunotherapy.

RESULTS:

In vitro assays demonstrated that PV001-DV possesses the ability to directly kill human melanoma cells lines as well as patient melanoma tissue ex vivo. Importantly, further work demonstrated that, when patient peripheral blood mononuclear cells (PBMCs) were exposed to PV001-DV, a substantial induction in the production of apoptotic factors and immunostimulatory cytokines was detected. When tumor cells were cultured with the resulting soluble mediators from these PBMCs, rapid cell death of melanoma and breast cancer cell lines was observed. These soluble mediators also increased dengue virus binding ligands and immune checkpoint receptor, PD-L1 expression.

CONCLUSIONS:

The direct in vitro tumor-killing and immune-mediated tumor cytotoxicity facilitated by PV001-DV contributes support of its upcoming clinical evaluation in patients with advanced melanoma who have failed prior therapy.

100 项与 PV001 相关的药物交易

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