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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Advanced Melanoma
- Sponsor
- PrimeVax Immuno-Oncology Inc.
- Enrollment
- 10
- Primary Endpoint
- Incidence and severity of Treatment-Emergent Adverse Events of PV-001-DV
- Status
- Not Yet Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Biopsy confirmed patients with un-resectable American Joint Committee on Cancer Stage III or IV melanoma who have measurable disease. Measurable disease is required, and is defined as tumor can be measured in one dimension along the longest diameter
- •Patients must have tumors that are not responsive having completed prior therapy with a Progressive Death-1/Progressive Death Ligand-1 (PD-1 / PD-L1), antagonist alone or in combination with anti-Cytotoxic T Lymphocyte Antigen-4 (CTLA-4). If the patient is positive for BRAF mutation, 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 must be progressing after having completed one standard of care therapy for metastatic melanoma
- •Tumor specimens must be available for tumor lysates and immunological studies.
- •Tumors must be available for intratumoral injection of dengue virus. This includes cutaneous and subcutaneous lesions with ultrasound-guided injection.
- •Eastern Cooperative Oncology Group Performance Status of ≤ 2 (corresponds to a Karnofsky Performance Status (KPS) of ≥ 70).
- •Patients must be 18 years or older and able to give informed consent.
- •Adequate bone marrow function of White Blood Cell (WBC) count to ≥ 1,500/microliter (uL); platelet count ≥ 100,000/mm3; absolute neutrophil count (ANC) \> 1,500/mm3
- •Patients must have adequate renal function by serum creatinine of ≤ 2.0 milligrams/decaliter (mg/dL).
- •Adequate hepatic function of bilirubin ≤ 2.5 mg/dL; Serum Glutamic Oxaloacetate Transaminase/Serum Glutamic Pyruvate Transaminase (SGOT/SGPT \< 3× upper limit of normal (ULN).
Exclusion Criteria
- •Patients with positive antibody (Ab), to any Dengue Virus serotype by tetravalent Enzyme Linked Immunosorbent Assay (ELISA).
- •Patients with prior vaccinations or positive Ab detected by ELISA to: West Nile, St. Louis Encephalitis, or Yellow Fever
- •Pre-existing autoimmune or antibody mediated disease including systemic lupus erythematous, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, but excluding controlled thyroid disease, or the presence of autoantibodies without clinical autoimmune disease.
- •Known history of human immunodeficiency virus (HIV) or any active immunosuppressive systemic infection or a suppressed immune system, including acquired immuno-deficiency syndrome (AIDS) or HIV positivity and known hepatitis infections C or B (HCV or HBC), as assessed by serology.
- •Patients on immunosuppressive therapy. Concurrent steroid use of not more than an equivalent of 10 mg of prednisone is allowed.
- •Any other open wounds.
- •Previous organ transplantation.
- •Patients with clinically significant dermatological disorders, as judged by the clinical investigator (e.g., eczema or psoriasis), any skin lesions or ulcers, any history of atopic dermatitis, or any history of Darier's disease (Keratosis Follicularis).
- •Patients with White Blood Cell count \<1,500/uL; platelet count \<100,000/mm3; absolute neutrophil count (ANC) 1,500/mm3 (Grade 2)
- •Patients with inadequate renal function by serum creatinine of \>1.5 x ULN (Grade 2)
Outcomes
Primary Outcomes
Incidence and severity of Treatment-Emergent Adverse Events of PV-001-DV
Time Frame: 365 days
Treatment-Emergent Adverse Event Incidence of patients receiving intratumoral injection of PV-001-DV
Secondary Outcomes
- Overall Survival (OS)(365 days)
- Overall Response Rate (ORR)(365 days)
- Progression-Free Survival (PFS)(365 days)