RNA-NP vaccine / University of Florida - LARVOL DELTA

UF-CUT-001: Novel RNA-lipid Particle (RNA-LP) Vaccine for Anti-PD-1 Antibody Therapy Sensitization (clinicaltrials.gov) - P1 | N=18 | Suspended | Sponsor: University of Florida | Trial completion date: Dec 2026 ➔ Jun 2027 | Recruiting ➔ Suspended | Trial primary completion date: Dec 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Trial suspension • Melanoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Focused ultrasound potentiates RNA nanoparticle immunotherapy in pediatric brain tumors (EANO 2026) - "We have developed a personalized mRNA-nanoparticle vaccine (RNA-NP; IND#19308) that drives antigen-specific immune activation through uptake by innate immune cells and subsequent priming of adaptive responses... LIFU is an effective, non-invasive strategy to overcome BBB-associated delivery barriers and enhance CNS uptake of RNA-NPs across aggressive pediatric brain tumors. Integration of scRNA-seq defines the cellular landscape of nanoparticle uptake and response, providing mechanistic insight into therapeutic activity. This combinatorial approach supports further development of nanoparticle-based immunotherapy to improve delivery, immune activation, and survival in CNS malignancies."

Clinical • IO biomarker • Brain Cancer • Diffuse Midline Glioma • Glioma • High Grade Glioma • Medulloblastoma • Oncology • Solid Tumor

UF-CUT-001: Novel RNA-lipid Particle (RNA-LP) Vaccine for Anti-PD-1 Antibody Therapy Sensitization (clinicaltrials.gov) - P1 | N=18 | Suspended | Sponsor: University of Florida | Trial completion date: Sep 2026 ➔ Dec 2026 | Recruiting ➔ Suspended | Trial primary completion date: Sep 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Trial suspension • Cutaneous Melanoma • Melanoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Novel RNA-nanoparticle Vaccine for the Treatment of Early Melanoma Recurrence Following Adjuvant Anti-PD-1 Antibody Therapy (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: University of Florida | Suspended ➔ Recruiting

Enrollment open • Melanoma • Oncology • Solid Tumor • BRAF

Novel RNA-nanoparticle vaccine for the treatment of early melanoma recurrence following adjuvant anti-PD-1 antibody therapy. (ASCO 2024) - P1 | "Based on the tolerability and efficacy across subjects with both BRAF mutated and wildtype melanoma anti-PD1 (aPD1) therapy with either nivolumab or pembrolizumab are considered first line treatment in this setting. The goal of this study is to assess safety, tolerability, and feasibility of tumor specific RNA-LPs. Important biological correlates will also be collected and analyzed including tumor tissue sampling at initial time of checkpoint resistance and following vaccination series to identify key changes to the TME and tumor induced by lipid-nanoparticle vaccine administration."

Clinical • IO biomarker • Melanoma • Oncology • Solid Tumor • BRAF

Novel RNA-nanoparticle Vaccine for the Treatment of Early Melanoma Recurrence Following Adjuvant Anti-PD-1 Antibody Therapy (clinicaltrials.gov) - P1 | N=18 | Suspended | Sponsor: University of Florida | Recruiting ➔ Suspended

Trial suspension • Melanoma • Oncology • Solid Tumor • BRAF

Novel RNA-nanoparticle Vaccine for the Treatment of Early Melanoma Recurrence Following Adjuvant Anti-PD-1 Antibody Therapy (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: University of Florida | Not yet recruiting ➔ Recruiting

Enrollment open • Melanoma • Oncology • Solid Tumor • BRAF

Novel RNA-nanoparticle Vaccine for the Treatment of Early Melanoma Recurrence Following Adjuvant Anti-PD-1 Antibody Therapy (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: University of Florida

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • BRAF

Novel RNA-nanoparticle vaccine for the treatment of early melanoma recurrence following adjuvant anti-PD-1 antibody therapy (SITC 2023) - P1 | "In this study we propose the use of subject derived RNA-LP vaccine in patients who progress on, or soon after completion of adjuvant ICI. Secondary endpoints include overall response rate (ORR) and progression free survival rate (figure 5). Exploratory analysis will investigate the TME through single cell analysis pre and post vaccine series."

Clinical • IO biomarker • Melanoma • Oncology • Solid Tumor • LAMP1

Novel RNA-nanoparticle Vaccine for the Treatment of Early Melanoma Recurrence Following Adjuvant Anti-PD-1 Antibody Therapy (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: University of Florida | Trial completion date: Jul 2027 ➔ Sep 2026 | Trial primary completion date: Jul 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • BRAF

Multilamellar mRNA lipid particles induce immunologic reprogramming in canine and human glioblastoma patients (SNO 2022) - P1 | "First-in-human application of systemic multilamellar RNA-NP vaccines results in significant biologic effects and rapid immunologic reprogramming."

Clinical • IO biomarker • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Immunology • Infectious Disease • Novel Coronavirus Disease • Oncology • Solid Tumor • CD8 • IL12A • IL6 • TLR7 • TNFA

RNA-nanoparticle vaccines overcome the immunosuppressive tumor microenvironment of metastatic osteosarcoma (SITC 2022) - P1 | "These vaccines bypass MHC restriction and can be made readily available for all patients/canines providing a renewable antigen resource that can be used to continuously vaccinate patients. This agent, which is FDA-IND approved (BB-19304, Sayour) and in human clinical trials for patients with brain tumors ( NCT04573140 ), may be a promising potential novel therapy for patients with recurrent pulmonary metastatic osteosarcoma."

Biomarker • IO biomarker • Tumor microenvironment • Brain Cancer • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • BATF3 • PTPRC

Novel RNA-nanoparticle Vaccine for the Treatment of Early Melanoma Recurrence Following Adjuvant Anti-PD-1 Antibody Therapy (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: University of Florida | Initiation date: Jan 2023 ➔ Jun 2023

Trial initiation date • Melanoma • Oncology • Solid Tumor • BRAF

Novel RNA-nanoparticle Vaccine for the Treatment of Early Melanoma Recurrence Following Adjuvant Anti-PD-1 Antibody Therapy (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: University of Florida | Initiation date: Oct 2022 ➔ Jan 2023

Trial initiation date • Melanoma • Oncology • Solid Tumor • BRAF

Novel RNA-nanoparticle Vaccine for the Treatment of Early Melanoma Recurrence Following Adjuvant Anti-PD-1 Antibody Therapy (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: University of Florida | Initiation date: May 2022 ➔ Oct 2022

Trial initiation date • Melanoma • Oncology • Solid Tumor • BRAF