Phase IIB TL + YCWP + DC in Melanoma

Summary

Objectives

Stage III and Stage IV (resected) melanoma patients will be identified prior to
definitive surgery and screened for inclusion/exclusion criteria. Eligible patients will
be counseled and consented for tissue procurement. Enrolled patients will have their
disease surgically resected and a portion 1mg minimum of their melanoma sterilely frozen
in provided freezing vials and storage tubes. This tissue will be shipped in liquid
nitrogen shippers through FedEx to our central facility in Greenville SC and stored
frozen until vaccine preparation. If patients cannot be rendered disease-free, they will
be considered screen failures for this study. If melanoma is being resected from multiple
locations primary and nodes two different metastatic sites then samples of each would be
preferred but not mandatory.

As indicated by SoC per the National Comprehensive Cancer Network (NCCN) guidelines and
determined by the treating team, if a patient is to receive systemic therapy
(chemotherapy or IFN-aguidelines) and determined by the treating team, if a patient is to
receive systemic therapy (chemotherapy or IFN-central facility in Greenville, SC) and
stored frozen until vaccine preparation. If patients cannot be rendered disease-free,
they will receive a single injection of Neupogen (G-CSF) 300 mod (or its equivalent) SQ
24-48 hrs. prior to having 70 mL of blood collected and sent to our central facility for
DC isolation and preparation. Patients who cannot tolerate Neupogen, or its equivalent or
refuse it, will have 120 mL of blood drawn and sent. Additional blood may be drawn if
additional vaccine doses need to be made or re-made for any reason. Vaccines will be
prepared by producing TL through freeze/thaw cycling and then loaded into pre-prepared
YCWP. The TL-loaded YCWP will be introduced to the DC for phagocytosis thus creating the
TLPLDC vaccine which will be frozen in single dose vials. Each vial will contain 1-1.5 x
106 TLPLDC and will be labeled with the patient's unique study number.

Based on their randomization, autologous TLPLDC (active vaccine) or unloaded YCWP +
autologous DC (control) will be sent back to the site in a blinded fashion. Regardless of
assigned group, the site will receive 6 single dose vials to be injected intradermal
monthly x 3 followed by boosters at 6, 12, and 18 months in the same lymph node draining
area (preferably the anterior thigh). Patients must begin vaccinations between 3 weeks
and 3 months from completion of (SoC). Frozen tumor will be maintained for active
vaccines for all patients to include the control patients. The latter will be offered
their active vaccine at time of recurrence in a crossover fashion. Additionally, control
patients who do not recur will be offered active vaccine at the completion of the trial.

Safety data will be collected on local and systemic toxicities and graded and reported
per the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

Disease-free status will be monitored per SoC as outlined by NCCN. Suspected recurrences
will be documented with biopsy and pathologic confirmation. Time to recurrence will be
based on date of randomization to time of confirmed recurrence.

Recurrent patients will be offered participation in the open label portion of the study.
New active vaccine will be made for all patients, and they will be inoculated at 0, 1, 2,
3, 6, and 9 mos. Patients will be treated per SoC for their recurrence. Safety and tumor
response will be assessed per RECIST and irRC on their SoC follow-up scans.

Blood (50 mL) will be collected from all patients prior to each inoculation and at 24
months from enrollment for a total of 7 time points or a total of 350 mL of blood over 2
years. The collected blood will be sent to our central facility for immunologic testing
of the T-cell response.