| Eligibility |
Inclusion Criteria:
- Willing and able to give written informed consent.
- Have histologically confirmed unresectable or metastatic melanoma having received no
more than one prior systemic therapy for the metastatic disease (eg. ipilumamab and/or
BRAF inhibitor); unresectable or metastatic smoking-associated NSCLC having received
no more than one prior systemic therapy for the metastatic disease (eg standard of
care chemotherapy, as appropriate); unresectable or metastatic transitional cell
carcinoma of the bladder, urethra, ureter or renal pelvis having received no more than
one prior systemic therapy for the metastatic disease.
- Have at least one site of disease measurable disease by RECIST v1.1 that has not been
treated with local therapy within 6 months of study treatment. This can be the site
for initial or repeat biopsies as long as it will remain measurable following biopsy.
- At least one site of disease must be accessible to provide repeat biopsies for tumor
tissue for sequence and immunological analysis.
- Have ECOG PS of 0 or 1 with an anticipated life expectancy of > 6 months.
- Age = 18 years.
- Recovered from all toxicities associated with prior treatment to acceptable baseline
status (for laboratory toxicity see below limits for inclusion) or National Cancer
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03,
Grade of 0 or 1, except for toxicities not considered a safety risk (e.g., alopecia or
vitiligo).
- Screening laboratory values must meet the following criteria and should be obtained
within 30 days (45 if biopsy is repeated) prior to study treatment:
- White blood cell (WBC) count = 3 × 10e3/µL
- Absolute neutrophil count (ANC) = 1.5 × 10e3/µL
- Absolute lymphocyte count (ALC) = 1 × 10e3/µL
- Platelet count = 100 × 10e3/µL
- Hemoglobin > 9 g/dL
- Serum creatinine = 1.5 × upper limit of normal (ULN) or creatinine clearance (CrCl) =
40 mL/min/1.73 m
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 × ULN
- Total bilirubin = 1.5 × ULN (except in patients with Gilbert Syndrome who can have
total bilirubin < 3.0 mg/dL).
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
[HCG]) within 7 days prior to the start of nivolumab.
- Female participants, who are not free from menses for >2 years, post hysterectomy /
oophorectomy, or surgically sterilized, must 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, from screening
through 5 months after the last dose of study treatment (including nivolumab single
agent). Approved contraceptive methods include, for example: intrauterine device,
diaphragm with spermicide, cervical cap with spermicide, male condom with spermicide,
or female condom with spermicide. Spermicides alone are not an acceptable method of
contraception.
- Men who are sexually active with women of child bearing potential must agree to use a
condom from screening through 7 months after the last dose of study treatment
(including nivolumab single agent).
- For NSCLC, patients must have a minimum of a 10 pack-year smoking history.
Exclusion Criteria:
- Received therapy with any immunotherapeutic agents including, but not limited to, any
anti-PD1 or anti-PDL1 antibody therapy, with these exceptions: Melanoma patients
having received and progressed on anti-CTLA4 (cyctotoxic T lymphocyte-associated
antigen 4) may participate in the trial; Bladder cancer patients having received
intra-vesical BCG may participate in the trial.
- Received systemic anti-cancer therapy within 30 days of Week 0, Day 11 of study
treatment.
- Have untreated central nervous system (CNS) metastases. Patients are eligible for
study participation if CNS metastases are adequately treated and patients are
neurologically returned to baseline (except for residual signs or symptoms related to
the CNS treatment) for at least 60 days prior to consent. In addition, patients must
either be off corticosteroids, or on a stable or decreasing dose of 10 mg daily
prednisone (or equivalent) for at least 60 days prior to consent.
- Received non-oncology vaccine therapy for prevention of infectious diseases during the
4-week period prior to first dose of nivolumab therapy. Patients may not receive any
non-oncology vaccine therapy during the period of NEO-PV-01 + adjuvant or nivolumab
administration and until at least 8 weeks after the last dose of the booster vaccine.
Annual influenza vaccines are allowed during screening and pre-treatment but not
during nivolumab or NEO-PV-01 + adjuvant dosing.
- Received radiation therapy within 4 weeks prior to Week 0, Day 1 of study treatment.
Patients may not receive or have received any radiation therapy at the biopsy sites.
- Have an active or history of autoimmune disease (known or suspected). Exceptions are
permitted for vitiligo, type I diabetes mellitus, residual hypothyroidism due to
autoimmune condition requiring only hormone replacement, psoriasis not on systemic
treatment, or conditions not expected to recur in the absence of an external trigger.
- Have a condition requiring systemic treatment with either corticosteroids (> 10 mg
daily prednisone equivalents) or other immunosuppressive medications within 15 days
prior to the first dose of study treatment (nivolumab). Inhaled or topical steroids
and adrenal replacement doses (= 10 mg daily prednisone equivalents) are permitted in
the absence of active autoimmune disease.
- Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C,
or life-threatening illnesses unrelated to cancer.
- Have an uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection requiring treatment, symptomatic congestive heart failure, unstable
angina pectoris, or cardiac arrhythmia.
- Have 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.
- Have a planned major surgery.
- Pregnant women are excluded from this study because nivolumab, personalized neoantigen
peptides, and Poly-ICLC are agents with unknown risks to the developing fetus.
- Nursing women are excluded from this study 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.
- Have a history of an invasive metastatic disease, except for the following
circumstances: individuals with a history of invasive metastatic disease are eligible
if they have been disease-free for at least 2 years and are deemed by the Investigator
to be at low risk for recurrence of that metastatic disease; 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.
- Mucosal melanoma and uvueal melanoma.
- Patients with NSCLC and known anaplastic lymphoma kinase (ALK) translocations or
epidermal growth factor receptor (EGFR) mutations who have not received prior
treatment with ALK or EGFR inhibitor.
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