Overview
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 progressed on anti-PD1 (a-PD1) adjuvant therapy.
Eligibility
Inclusion Criteria:
- Adults ≥ 18 years old
- Must have evidence of progressive disease (PD) by RECIST 1.1 criteria while receiving adjuvant aPD1 therapy, or progression within 6 months after completing adjuvant treatment for stage IIB-IV melanoma
- Must have received either PD1 or combination aPD1/CTLA-4 inhibition as adjuvant treatment for stage IIB-IV melanoma following surgical resection
- Must be BRAF wildtype
- ECOG performance ≤ 1
- Lab values within the specified ranges:
- Serum direct bilirubin ≤ 1.5 x ULN (upper limit of normal)
- 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 amendable to surgical sampling for RNA-NP vaccine
development
- 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. Subject agrees to comply with all the study-related procedures.
- Female subjects of childbearing potential must have a negative serum pregnancy test at screening
- Women of childbearing potential (WOCBP) 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.
WOCBP includes any woman who has experienced menarche and who has not undergone successful
surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)
or who is not post-menopausal Post-menopause is defined as:
- Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or
- For women with irregular menstrual periods who are taking hormone replacement therapy
(HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35
mIU/mL.
- 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
Exclusion Criteria:
- Subjects that have an active second malignancy, however, previously treated early
stage malignancies (non-melanoma skin cancers, ductal carcinoma in situ, or prostate
confined prostate cancer) with no evidence of disease recurrence after 5 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
- 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
- Subjects with uncontrolled infection requiring parenteral antibiotics, antivirals, or
antifungals within seven days prior to tissue collection for vaccine creation or
within even 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
- Clinically relevant active autoimmune disease
- Symptomatic congestive heart failure (NYHA 3 or 4)
- Subjects with unstable angina pectoris
- Subjects who are post-splenectomy
- Known hypersensitivity to the active substance or to any of the excipients
- Subjects with 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
- Females or males of childbearing potential who are unwilling or unable to use an
acceptable method to avoid pregnancy for the entire study period and for at least 4
months after the last dose of study treatment
- Females who are confirmed to be pregnant or breastfeeding
- History of any other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of protocol therapy or that might affect the interpretation of
the results of the study or that puts the subject at high risk for treatment
complications, in the opinion of the treating physician
- Administration of a vaccine containing live virus within 30 days prior to the first
dose of trial treatment. Note: Most flu vaccines are killed viruses, with the
exception of the intra-nasal vainer (Flu-Mist) which is an attenuated live virus and
therefore prohibited for 30 days prior to first dose. Non-live versions of the COVID
vaccine are allowed.
- Prisoners or subjects who are involuntarily incarcerated, or subjects who are
compulsorily detained for treatment of either a psychiatric or physical illness.