| Eligibility |
Inclusion Criteria:
- Patients must meet the following criteria on screening examination to be eligible to
participate in the study:
- Patient is willing and able to give written informed consent.
- Patient is agreeable to allow tumor and normal tissue samples to be submitted for
complete exome and transcriptome sequencing.
- Pathologically confirmed, clinically evident (by physical examination or radiographic
imaging) stage IIIB, IIIC, and IVM1a and b cutaneous melanoma (anatomic stages T1-4b
N1a and T1-4b N2a not included). ) The current diagnosis may be the patient's first
diagnosis of melanoma or recurrent melanoma after previous diagnosis of an earlier
stage melanoma.
- Complete surgical resection of metastatic disease (lymph node, in transit, satellite
lesion(s), distant metastastases) with negative margins on resected specimens as
confirmed by pathologic review has not been performed, but is deemed feasible by the
treating surgical oncologist. Surgical resection of the primary melanoma may or may
not have been performed.
- The patient must be free of unresectable metastatic disease within 4 weeks prior to
the surgery being performed with the intention to remove all melanoma.
- This pre-surgery baseline assessment must be documented by complete physical
examination and imaging studies. Imaging studies must include a total body PET-CT in
conjunction with a brain MRI (or head CT if brain MRI is contraindicated). If a PET/CT
scan cannot be done, a CT of the neck, chest, abdomen, and pelvis should be performed.
- Patients may have received prior interferon alpha (IFN-a), but must have discontinued
IFN-a therapy within 4 weeks prior to enrollment on the trial. - Patients who have not
received prior adjuvant therapy should be informed of the potential therapeutic
benefit of IFN-a. Previous radiation therapy, including after the surgical resection,
is allowed as long as 14 days have elapsed between the radiation and initiation of
first vaccination with NeoVax.
- Age = 18 years.
- ECOG performance status <1
- Normal organ and bone marrow function as defined below:
- Leukocytes = 3,500/mcL
- Absolute lymphocyte count > 800/mcL
- Absolute neutrophil count > 1,500/mcL
- Platelets > 100,000/mcL
- Hemoglobin > 10.0 g/dL
- Total serum bilirubin < 1.0 x institutional upper limit of normal
- AST (SGOT)/ALT (SGPT) < 2.0 x institutional upper limit of normal
- Serum creatinine< 1.5 x institutional upper limit of normal
- Women of childbearing potential (WOCBP) must have a negative pregnancy test (minimum
sensitivity 25 IU/L or equivalent of HCG) before entry onto the trial and within 7
days prior to start of study medication, because the effects NeoVax on the developing
human fetus are unknown. It is the investigators' responsibility to repeat the
pregnancy test should start of treatment be delayed.
- Female patients enrolled in the study, 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, starting
with visit 1 through 4 weeks 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.
- Male patients must agree to use an adequate method of contraception starting with the
first dose of NeoVax through 4 weeks after the last dose of study therapy.
Exclusion Criteria:
- Prior treatment with immune-modulatory agents including, but not limited to: IL-2,
CTLA-4 blockade, PD-1/PD-L1 blockade, CD40 stimulation, CD137 stimulation with the
exception of INF-a given as adjuvant treatment for high-risk, surgically resected
melanoma
- Prior investigational melanoma-directed cancer vaccine therapy
- Prior chemotherapy, including targeted therapy such as BRAF or MEK inhibition
- Treatment with other investigational products within the last 2 months prior to entry
into this study
- Previous bone marrow or stem cell transplant
- Concomitant therapy with any anti-cancer agents, other investigational anti-cancer
therapies, or immunosuppressive agents; chronic use of systemic corticosteroids
- Use of a non-oncology vaccine therapy for prevention of infectious diseases (up-to) 4
weeks prior to enrollment to the study. Patients may not receive any non-oncology
vaccine therapy during the period of NeoVax administration and until at least 8 weeks
after the last dose of study therapy
- History of severe allergic reactions attributed to any vaccine therapy for the
prevention of infectious diseases
- Mucosal melanoma and uveal melanoma are not allowed
- Active, known, or suspected autoimmune disease or immunosuppressive conditions with
the exception of vitiligo, type 1 diabetes, residual autoimmune-related hypothyroidism
requiring hormone replacement, or psoriasis not requiring systemic treatment.
- Concomitant treatment with corticosteroids greater than physiologic doses (used in the
management of cancer or non-cancer-related illnesses). Topical (if not including the
proposed vaccination sites) or inhalational steroids are allowed.
- Known chronic infections with HIV, hepatitis B or C
- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia
- 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.
- Pregnant women are excluded from this study because 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 personalized neoantigen peptides and poly-ICLC, nursing
women are excluded from this study.
- Individuals with a history of a different malignancy are ineligible except for the
following circumstances: Individuals with a history of other malignancies are eligible
if they have been disease-free for at least 5 years and are deemed by the investigator
to be at low risk for recurrence of that malignancy. Individuals with the following
cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer
in situ and basal cell or squamous cell carcinoma of the skin
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