Melanoma Clinical Trials

• Adults ≥ 18 years old

• ECOG performance ≤ 2

• Lab values within the specified ranges:

‣ Hemoglobin ≥ 8G/DL

⁃ Platelets ≥ 100 thou/cumm

⁃ Absolute Neutrophil Count (ANC) ≥ 1000 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 measurable 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.

• Participants of childbearing potential must have a negative serum pregnancy test at screening

• Participants 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, participants of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.

• Subjects with 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:

• Patients with stage II, stage III, or resected stage IV melanoma who received anti-PD-1-based therapy in the adjuvant or neoadjuvant setting (either monotherapy or combination therapy) and experienced progressive disease (PD) per RECIST 1.1 during treatment or within 6 months of completing the planned course of therapy. This includes patients who:

‣ Were planned to receive approximately 1 year of anti-PD-1-based therapy in the adjuvant setting but discontinued early due to toxicity and relapsed within 6 months of discontinuation;

⁃ Received neoadjuvant anti-PD-1-based therapy (with or without subsequent surgery), including patients planned to complete approximately 1 year of total perioperative anti-PD-1-based therapy (neoadjuvant ± adjuvant), and experienced PD during therapy or within 6 months of completion or discontinuation;

⁃ Received short-course neoadjuvant anti-PD-1-based therapy (including combination regimens), underwent surgery, were subsequently managed with surveillance (including those achieving pathologic complete response), and experienced relapse within 6 months of completion of neoadjuvant therapy.

• Patients with unresectable or widespread metastatic (stage IV) melanoma who experienced PD per treating physician while receiving anti-PD-1-based therapy (either monotherapy or combination therapy) in any line of treatment.

• Patients with unresectable or widespread metastatic (stage IV) melanoma who:

‣ Completed a planned course of anti-PD-1-based therapy (monotherapy or combination), including planned treatment durations of approximately 1 year or 2 years, and experienced PD within 6 months of completion; or

⁃ Were planned to receive anti-PD-1-based therapy (for either 1 year or 2 years) but discontinued early due to toxicity and experienced PD within 6 months of discontinuation.

• Both cutaneous and non-cutaneous melanoma subtypes (including uveal, mucosal, and acral lentiginous) are eligible.

• Patients must:

‣ Have no contraindication to continued immune checkpoint therapy;

⁃ Not have rapidly progressive disease requiring urgent alternative therapy; and

⁃ Have no other viable approved salvage treatment options available, or decline currently approved salvage therapies.

∙ Additional eligibility criteria for subjects with soft tissue sarcoma:

• Evidence of spindle cell, pleomorphic, round cell, or epithelioid morphology on pathology suggestive of sarcoma as determined by a sarcoma pathologist

• Evidence of progression or resistance to therapy as defined by the treating physician.

• Must have measurable disease per RECIST 1.1

• 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 with prior exposure to an immune checkpoint inhibitor (ICI) are eligible for enrollment; however, prior ICI therapy is not required unless receipt of an ICI constitutes part of the FDA-approved standard of care for their disease.