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

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 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.
• •Additional eligibility criteria for subjects with melanoma:
• •Must have measurable disease with evidence of progression (progressive disease, or 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
• •Patients with stage IV nonresectable disease with rare melanoma subtypes: (mucosal, acral, uveal, non-sun exposed) are eligible for the study if they fail to response to initial immunotherapy given in the first line metastatic setting. These rare subtypes do not respond to aPD1 blockade at the same rate or degree as cutaneous melanomas and behave more like adjuvant failure patients in response to aPD1. These patients must have disease amenable to sampling and in the opinion of the treating physician have appropriate bridging therapy available to reach vaccination series, have no other approved therapeutic options/or decline their use.
• •Patients of any stage treated with immune checkpoint inhibition with primary or secondary immunotherapy resistance. Primary resistance is defined as a minimum drug exposure requirement of 8-12 weeks or roughly two doses of the immunotherapy with Lack of benefit defined as progressive disease at the time of the first planned assessment or stable disease lasting less than 6 months. Secondary resistance is defined as exposure to immune checkpoint inhibition for at least 6 months with best response initially including a complete response, partial response, or stable disease lasting for greater than 6 months with subsequent progression while receiving checkpoint inhibition, or within 6 months of completing a planned course of immunotherapy. These patients are eligible for enrollment if their disease is amenable to sampling for vaccine generation and they are not contraindicated to continuation of immune checkpoint therapy, and do not have rapidly progressing disease, and have no other viable clinical options or choose not to pursue current approved salvage options for therapy.
• •Must have received either aPD1, combination aPD1/CTLA-4 inhibition, or PD1/LAG-3 inhibitor as adjuvant or definitive metastatic treatment for stage IIB-IV melanoma following surgical resection
• •Must be BRAF wildtype, or have BRAF mutation but contra-indication to BRAF/MEK inhibitor use, have progressed while on BRAF/MEK therapy, or decline the option to utilize BRAF/MEK therapy.
• •Additional eligibility criteria for subjects with soft tissue sarcoma:
• •Must have measurable disease and tumor accessible for tissue sampling
• •Evidence of spindle cell, pleomorphic, round cell, or epithelioid morphology on pathology suggestive of sarcoma as determined by a sarcoma pathologist
• •Original tumor site from soft tissue location i.e. lipomatous tissue, musculature, skin
• •Evidence of unresectable stage II disease; stage III or stage IV disease
• •Subjects may be eligible without receiving prior therapy if no FDA approved or standard of care therapy is indicated/available
• •Subjects with prior immune checkpoint inhibitor exposure may be eligible, but prior exposure is not required unless it is a component of an FDA approved indication