Novel RNA-lipid Particle (RNA-LP) Vaccine for Anti-PD-1 Antibody Therapy Sensitization
University of Florida
Summary
The goal of this phase I trial is to evaluate the toxicity and feasibility of a tumor-specific RNA-NP vaccine in patients with stage IIB-IV melanoma who have evidence of progressive disease by RECIST 1.1 criteria while receiving adjuvant aPD1 therapy, or those who progress within 6 months of completion of adjuvant treatment, or unresectable stage II soft tissue sarcoma or stage III-IV soft tissue sarcoma.
Description
Melanoma is an increasing public health concern in the state of Florida. The advent of immune checkpoint inhibitors (ICI) has revolutionized the treatment of advanced melanoma. Unfortunately, in the adjuvant setting, up to 30% of subjects will have disease recurrence within 1 year of starting ICI therapy. Previous studies have shown that subjects who progress while on adjuvant ICI treatment, or soon after completion, have a more aggressive course of disease that responds poorly to subsequent immunotherapy. One reason for the failure of ICI in the post adjuvant setting is the immune suppressive…
Eligibility
- Age range
- 18–99 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Adults ≥ 18 years old * ECOG performance ≤ 2 * Lab values within the specified ranges: * Hemoglobin ≥ 8G/DL * Platelets ≥ 100 thou/cumm * Absolute Neutrophil Count (ANC) ≥ 1000 thou/cumm * Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) * AST and ALT ≤ 2.5 x ULN; If confirmed liver metastases: AST and ALT ≤ 5 x ULN * Creatinine clearance (CrCl) ≥ 15 ml/min (based on modified Cockcroft and Gault formula) * Must have measurable disease that is amenable to surgical sampling for RNA extraction, amplification, and loading of lipid particles * Subjects m…
Interventions
- BiologicalAutologous total tumor mRNA loaded DOTAP liposome vaccine
All participants will receive three doses of RNA-LP vaccine (1 dose every 2 weeks) intravenously. The vaccine dose given will be determined by a 3 + 3 design with cohort sizes of 3 participants. Cohorts will be agnostic of disease indication. Participants will be given one of the following vaccine doses: Dose Level -2: 0.00015625 mg/kg of mRNA encapsulated in 0.00234375 mg/kg lipid particles (LPs) Dose Level -1 (Starting Dose Level): 0.0003125 mg/kg of mRNA encapsulated in 0.0046875 mg/kg LPs Dose Level 0: 0.000625 mg/kg of mRNA encapsulated in 0.009375 mg/kg LPs Dose Level 1: 0.00125 mg/kg mRNA encapsulated in 0.01875 mg/kg LPs Dose Level 2: 0.0025 mg/kg mRNA encapsulated in 0.0375 mg/kg LPs
Location
- University of FloridaGainesville, Florida