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 ≥ 150 thou/cumm * Absolute Neutrophil Count (ANC) ≥ 1500 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 disease that is amenable to surgical sampling for RNA extraction, amplification, and loading of lipid particles * Subjects must not hav…
Interventions
- BiologicalAutologous total tumor mRNA loaded DOTAP liposome vaccine
All participants will receive three doses of RNA-NP vaccine (1 dose every 2 weeks) intravenously. The vaccine dose given will be determined by a 3 + 3 design. Participants will be given one of the following vaccine doses: Dose level 0 (starting dose level): 0.00125 mg/kg mRNA in 0.01875 mg/kg LP; Dose level 1: 0.0025 mg/kg mRNA in 0.0375 mg/kg LP; Dose level 2: 0.005 mg/kg mRNA in 0.075 mg/kg LP; or Dose level 3: 0.01 mg/kg mRNA in 0.15 mg/kg LP If 3 or more of the initial 6 subjects experience a dose-limiting toxicity, then the initial starting dose will be reduced (dose de-escalation) to 0.000625 mg/kg mRNA encapsulated in 0.009375mg/kg LPs (Dose level -1).
Location
- University of FloridaGainesville, Florida