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.