Neoantigen Vaccine (NeoVax plus Montanide) in Combination with Nivolumab and Ipilimumab for the Treatment of Unresectable Melanoma

Inclusion Criteria

• Participant is willing and able to give written informed consent
• Participants must have histologically confirmed stage IIIB/C/D or stage IV cutaneous melanoma (mucosal melanoma or uveal melanoma are excluded) that is surgically resected, is deemed surgically resectable, or is unresectable; tumor tissue for sequence analysis must be available from either previous melanoma resection/biopsy or at least one site of disease must be amenable to surgical or core biopsy
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Recovered from all toxicities associated with prior treatment, to acceptable baseline status (as to lab toxicity see below limits for inclusion) or a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0, grade of 0 or 1, except for toxicities not considered a safety risk, such as alopecia or vitiligo
• White blood cells (WBC) >= 3,000/uL
• Absolute neutrophil count (ANC) >= 1,500/uL
• Platelets >= 100,000/uL
• Hemoglobin ˃ 9.0 g/dL
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x ULN
• Creatinine =< 1.5 x ULN OR creatinine clearance >= 40 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
• Women of childbearing potential (WOCBP) should have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab, because the effects of NeoVax plus montanide and nivolumab on the developing human fetus are unknown
• Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study agents, breastfeeding should be discontinued if the mother is treated with ipilimumab, nivolumab and NeoVax + montanide
• Female participants enrolled in the study, who are not free from menses for > 2 years, post hysterectomy / oophorectomy, or surgically sterilized, should be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity throughout the study, starting with visit 1 through 5 months after the last dose of study therapy. Approved contraceptive methods include for example: intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. The investigational product will be permanently discontinued in an appropriate manner

Exclusion Criteria

• Prior immunotherapy except for anti-CTLA-4. Patients with unresectable melanoma who have received PD-1 inhibition therapy as adjuvant therapy and stopped receiving PD1 inhibition for a period of 6 months before starting treatment with nivolumab are allowed to participate
• > 24 weeks between surgical resection of stage IIIB/C/D or IV melanoma and initiation of study treatment
• Concomitant therapy with any anti-cancer agents, other investigational anti-cancer therapies, or immunosuppressive agents including but not limited to methotrexate, chloroquine, azathioprine, etc. within six months of study participation
• Active brain metastases or leptomeningeal metastases
• Use of a non-oncology vaccine therapy for prevention of infectious diseases (with the exception of vaccination against the SARS-CoV-2 virus for the prevention of COVID-19 disease) during the 4 week period prior to first dose of nivolumab. Participants may not receive any non-oncology vaccine therapy during the period of nivolumab or NeoVax plus montanide administration and until at least 8 weeks after the last dose of study therapy. Given the severity of the COVID-19 pandemic, vaccination specifically against the SARS-CoV-2 virus for the prevention of COVID-19 is ALLOWED in this study
• History of severe allergic reactions attributed to any vaccine therapy for the prevention of infectious diseases
• Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Corticosteroids used as pre-medication for imaging studies are allowed
• Test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Known sensitivity or allergy to nivolumab and/or ipilimumab
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring treatment, symptomatic
• Any underlying medical condition, psychiatric condition or social situation that in the opinion of the investigator would compromise study administration as per protocol or compromise the assessment of adverse events (AEs)
• Planned major surgery (excluding surgery for resection of melanoma if applicable)
• Pregnant women are excluded from this study because nivolumab, personalized neoantigen peptides and poly-ICLC are agents with unknown risks to the developing fetus. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with nivolumab, personalized neoantigen peptides and poly-ICLC, nursing women are excluded from this study
• Individuals with a history of an invasive malignancy are ineligible except for the following circumstances: a) individuals with a history of invasive malignancy are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; b) individuals with the following cancers are eligible if diagnosed and treated - carcinoma in situ of the breast, oral cavity or cervix, localized prostate cancer, basal cell or squamous cell carcinoma of the skin
• Prisoners, or subjects who are compulsory detained are not eligible to participate