AN OPEN-LABEL, PHASE I STUDY OF NEO-PTC-01 IN PATIENTS WITH ADVANCED OR METASTATIC MELANOMA

In order to be eligible to participate in this study, a patient must meet all
of the following criteria:
1. Adult (age 18 to 75) men and women willing and able to give written informed
consent.
2. Histologically confirmed unresectable or metastatic melanoma.
3. Part 1:
a. Have previously received a PD-1/PD-L1 inhibitor (either as single agent or
in combination) and a CTLA-4 inhibitor-containing regimen (single agent or
combination) prior to NEO-PTC-01, with disease progression following these
therapies or otherwise lack of clinical benefit as determined by the study
investigator.

Note: Patients who have received a PD-1/PD-L1 inhibitor and ipilimumab (CTLA-4
inhibitor) are eligible. Patients who have discontinued a PD-1/PD-L1 or a
CTLA-4 inhibitor due to toxicity and those who are deemed not appropriate to
receive a CTLA-4 inhibitor are eligible (except for Part 1 cohort patients to
receive additional αPD-1 therapy).
4. Part 2:
a. Have received/are currently receiving a PD-1/PD-L1 inhibitor (as a single
agent or in combination with CTLA-4) for at least 3 months.
b. Have documented SD by RECIST 1.1 or clinically asymptomatic progressive
disease on the most recent imaging assessment, which must have occurred within
3 months of enrollment.
c. In the opinion of the investigator, are medically eligible and able to
continue with PD-1/PD-L1 inhibitor therapy.
d. In the opinion of the investigator, would benefit from the addition of a
T-cell-based therapy.
5. For known BRAF mutant patients: Patients must have also received targeted
therapy (B-raf inhibitor or B-raf/MEK combination therapy) prior to NEO-PTC-01,
unless deemed not appropriate to receive these treatments by the investigator.
6. Have at least 1 site of measurable disease by RECIST 1.1.
7. At least 1 site of disease must be accessible to biopsy for tumor tissue for
sequence and immunological analysis. The biopsy site may be the same as the
measurable site so long as it remains measurable. Surgical resection of the
measurable site may not be performed if that site is the only measurable
lesion. An archival biopsy may be used in place if the biopsy was taken within
6 months of informed consent.
8. Have ECOG PS of 0 or 1.
9. Recovered from all toxicities associated with prior treatment to acceptable
baseline status (for laboratory toxicities see below limits for inclusion) or
an NCI CTCAE version 5.0, Grade of 0 or 1, except for toxicities not considered
by the treating physician to be a safety risk (eg, alopecia).
10. Screening laboratory values must meet the following criteria and should be
obtained prior to any production phase assessments:
a. White blood cell (WBC) count >= 3 × 103/µL.
b. Absolute neutrophil count (ANC) >= 1.5 × 103/µL.
c. Platelet count >= 100 × 103/µL.
d. Hemoglobin > 9 g/dL or 6 mmol/L.
e. Serum creatinine <= 1.5 × upper limit of normal (ULN) or creatinine clearance
>= 50 mL/min by Cockcroft-Gault.
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3 ×
ULN.
g. Total bilirubin <= 1.5 × ULN (except in patients with Gilbert Syndrome, who
can have total bilirubin < 3.0 mg/dL).
h. International normalized ratio (INR), prothrombin time (PT), or activated
partial thromboplastin time (aPTT) <= 1.5 × ULN unless the patient is receiving
anticoagulant therapy, as long as PT or aPTT is within therapeutic range of
intended use of anticoagulants.

A potential patient who meets any of the following criteria will be excluded
from participation in this study:
1. Age greater than 75 years or less than 18 years.
2. Received more than 3 prior lines of therapy for metastatic disease.
3. 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 requiring systemic treatment, or conditions not expected to recur
in the absence of an external trigger.
4. Have known active central nervous system metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate
provided they are stable (without evidence of progression by imaging [using the
identical imaging modality for each assessment, either MRI or CT scan] for at
least 4 weeks prior to enrollment and any neurologic symptoms have returned to
baseline), have no evidence of new or enlarging brain metastases, and are not
using steroids for at least 7 days prior to enrollment. This exception does not
include carcinomatous meningitis, which is excluded regardless of clinical
and/or radiographic stability.
5. Active systemic infections requiring IV antimicrobial therapy, coagulation
disorders or other active major medical illnesses of the cardiovascular,
respiratory, or immune system, as evidenced by a positive stress thallium or
comparable test, myocardial infarction, clinically significant cardiac
arrhythmias such as uncontrolled atrial fibrillation, ventricular tachycardia,
or second- or third-degree heart block, and obstructive or restrictive
pulmonary disease.
6. Active major medical illnesses of the immune system including conditions
requiring systemic treatment with either corticosteroids (> 10 mg daily
prednisone equivalents) or other immunosuppressive medications within 14 days
prior to NEO PTC 01 infusion. Inhaled or topical steroids and adrenal
replacement doses (<= 10 mg daily prednisone equivalents) are permitted in the
absence of active autoimmune disease.
7. Known HIV infection, active chronic hepatitis B or C, and/or
life-threatening illnesses unrelated to cancer that could, in the
investigator*s opinion, interfere with participation in this study.
8. Have any underlying medical condition, psychiatric condition, or social
situation that, in the investigator*s opinion, would interfere with
participation in the study.
9. Have a planned major surgery that is expected to interfere with study
participation or confound the ability to analyze study data.
10. Are pregnant or breastfeeding, or expecting to conceive or father children
within the projected duration of the study, starting with the Screening visit
through 120 days after the EOT visit. Nursing women are excluded from this
study because there is an unknown but potential risk of AEs in nursing infants
secondary to treatment of the mother with treatments to be administered in this
study.
11. Have a history of another invasive malignancy aside from melanoma, except
for the following circumstances:
a. Patient has been disease-free for at least 2 years and is deemed by the
investigator to be at low risk for recurrence of that malignancy.
Patient was not treated with systemic chemotherapy for carcinoma in situ of the
breast, oral cavity, or cervix, basal cell, or squamous cell carcinoma of the
skin.