Novel RNA-lipid Particle (RNA-LP) Vaccine for Anti-PD-1 Antibody Therapy Sensitization

NCT05264974 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: UF-CUT-001IRB202200462OCR41806
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Melanoma; Soft Tissue Sarcoma

Keywords

melanoma; immunotherapy; vaccines; RNA-NP; soft tissue sarcoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose

  Determine the maximum tolerated dose of RNA-NP vaccine

  2 months

• Feasibility of treatment with RNA-NP vaccine

  Determine the feasibility of treatment with RNA-NP vaccine, defined as the percentage of subjects who undergo tumor sampling and vaccine generation who can have sufficient vaccine produced for treatment across the full three dose vaccination series and within a time window of 4 weeks from time of tumor sampling to vaccine delivery for use.

  4 weeks

Secondary Outcomes (2)

• Overall response rate

  4 weeks

• Progression-free survival

  5 years

Study Arms (1)

mRNA-nanoparticle (mRNA-NP) vaccine

EXPERIMENTAL

Biological: Autologous total tumor mRNA loaded DOTAP liposome vaccine

Interventions

Autologous total tumor mRNA loaded DOTAP liposome vaccine BIOLOGICAL

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).

Also known as: mRNA-NP (nanoparticle) vaccine

mRNA-nanoparticle (mRNA-NP) vaccine

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 have more than one active malignancy at the time of enrollment (subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen \[as determined by the treating physician and approved by the PI\] may be included)
• Written informed consent obtained from the subject.
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening
• Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least four months after the last dose of study treatment to minimize the risk of pregnancy. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
• Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for four months following the last dose of study treatment and must agree to not donate sperm during the study treatment period or for four months following the last dose of study treatment.

You may not qualify if:

• Subjects that have an active second malignancy, however, previously treated early stage malignancies with no evidence of disease recurrence after 3 years of follow-up will be allowed
• Subjects with a history of immune-mediated treatment-related adverse reactions leading to discontinuation of prior aPD1 therapy or severe hypersensitivity reaction to any monoclonal antibody or any other baseline risk in the opinion of the investigator that precludes continued use of aPD1 therapy
• If patients develop new brain metastases during the time between tumor sampling and vaccine generation and administration, patients may remain on study as long as they can receive definitive stereotactic radiosurgery or surgery to brain metastases and be able to resume systemic therapy within 6 weeks of discovery of new brain metastases.
• Subjects who received an investigational drug in another clinical trial must wait 28 days or at least 5 half-lives of the study drug, whichever is shorter, prior to enrollment in this study
• Patients must not have required corticosteroids (anything greater than 10mg of prednisone of equivalent, daily) or other immunosuppressive medications within 14 days of the start of trial treatment.
• Subjects with uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within seven days prior to tissue collection for vaccine creation or within seven days prior to vaccine administration (subjects on prophylactic agents are acceptable)
• Subjects with any life-threatening illness, medical condition, or organ system dysfunction, which in the investigator's opinion, could compromise subject safety
• Subjects with known active hepatitis B virus or untreated hepatitis C virus. Patients with previous history of hepatitis C who completed treatment for HCV would not be excluded as long as they have no detectable viral load.
• Clinically relevant active autoimmune disease that would pose significant risk to the patient's life should a flare ensue. Patients with chronic autoimmune rheumatologic endocrine, or psoriatic skin diseases may still be eligible pending they are not receiving systemic immunosuppression at the time of treatment as previously described and that patients are aware of the increased risk of flare provocation with treatment.
• Symptomatic congestive heart failure (NYHA Class 3 or 4)
• Subjects with unstable angina pectoris
• Subjects who are post-splenectomy, otherwise asplenic, or have moderate to severe splenomegaly (defined as a spleen larger than 13 cm in cranial-caudal height or longest diameter)
• Personal history of anaphylactic reaction to previous vaccination
• Known hypersensitivity to the active substance or to any of the excipients
• Subjects with known human immunodeficiency virus with CD4+T cells ≤ 350 cells/ul, a positive viral load as determined by institutional standard testing, or a history of AIDS defining opportunistic infection within the last 12 months

Sponsors & Collaborators

• University of Florida: lead
• Florida Department of Health: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32608, United States

RECRUITING

Related Publications (1)

• Villanueva MT. RNA delivery heats up cold tumours. Nat Rev Drug Discov. 2024 Jul;23(7):497. doi: 10.1038/d41573-024-00098-0. No abstract available.

  PMID: 38858569 DERIVED

MeSH Terms

Conditions

Melanoma; Sarcoma

Interventions

Nanoparticles; Vaccines

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Nanostructures; Manufactured Materials; Technology, Industry, and Agriculture; Biological Products; Complex Mixtures

Study Officials

• Leighton Elliott, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karine Charles

CONTACT

352-294-5018; kmcharles@ufl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2022
• First Posted: March 3, 2022
• Study Start: March 17, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

US (1)