Inclusion Criteria:
Eligibility to participate will be assessed at one timepoint: prior to initial core
needle/surgical biopsy (Initial Registration).
- - 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.
- - 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.
- - Participants must have normal organ and marrow function as defined below:
- WBC ≥3,000/µL.
- - Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can
have total bilirubin < 3.0 mg/dL)
- AST(SGOT)/ALT(SGPT) ≤ 3 x ULN.
- - Creatinine ≤ 1.5 x ULN OR.
- - Creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine
levels above institutional normal (if using the Cockcroft-Gault formula
below):
Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL.
Male CrCl = (140
- - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL.
- - Women of childbearing potential (WOCBP) should have a negative serum pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the
start of Nivolumab or Pembrolizumab, because the effects of NeoVax plus Montanide and
Nivolumab (or Pembrolizumab) 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 Nivolumab or Pembrolizumab, Personalized
Neoantigen vaccine, and CDX-301.
- - 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 or her partner is
participating in this study, she should inform her treating physician immediately.The
investigational product will be permanently discontinued in an appropriate manner.
- - Male participants should agree to use an adequate method of contraception starting
with visit 1 through 7 months after the last dose of study therapy.
Exclusion Criteria:
- - Prior immunotherapy for metastatic melanoma except for anti-CTLA-4.
Patients with
unresectable melanoma who have received PD-1 inhibition therapy as adjuvant therapy
and stopped receiving PD-1 inhibition for a period of ≥ 6 months before starting
treatment with Nivolumab or Pembrolizumab are allowed to participate.
- - 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 or Pembrolizumab.
Participants may not receive any non-oncology vaccine therapy during the period of
Nivolumab (or Pembrolizumab) or NeoVax plus CDX-301 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, Pembrolizumab, or CDX-301.
- - 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 AEs.
- - Planned major surgery (except for surgery for resection of melanoma if applicable).
- - Patients with known mutations/amplifications in Flt-3.
- - 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
