Vigil + Irinotecan and Temozolomide in Ewing's Sarcoma

Participants will be managed in an outpatient setting. Hematologic function, liver enzymes,
renal function and electrolytes will be monitored. Blood for immune function analyses
including IFNγ-ELISPOT analysis of cytotoxic T cell activation in response to autologous
tumor antigens will be collected at tissue procurement, post-procurement screening and Day 1
(prior to chemotherapy administration) at Cycles 2, 4, and 6, end of treatment (EOT), 3
months after EOT, and every 6 months thereafter. Blood for ctDNA analysis will be collected
at tissue procurement, prior to chemotherapy administration at baseline and on Day 1 prior to
chemotherapy administration at Cycles 2, 3, 4, and 6, and EOT.

Tissue Procurement Inclusion Criteria:

1. Histologically confirmed Ewing's Sarcoma Family of Tumors (ESFT).

2. Age ≥ 2 years.

3. Estimated survival ≥ 6 months.

4. Evidence of EWS translocation by FISH or RT-PCR or Next Generation Sequencing (NGS).
If available, NGS sequencing report should be submitted to Gradalis.

5. Recurrence or refractory to 1 line of systemic chemotherapy, including but not limited
to doxorubicin, vincristine, and ifosfamide.

6. Planned standard of care surgical procedure (e.g., tumor biopsy or palliative
resection or thoracentesis) and expected availability of a cumulative soft-tissue mass
of ~10-30 grams tissue ("grape" to "golf-ball" size / approximately 2 cm total
diameter on imaging) or pleural fluid estimated volume ≥ 500mL (from a primary or
secondary thoracentesis, yielding in a high volume of tumor cells) for immunotherapy
manufacture.

7. Tumor intended for immunotherapy manufacture is not embedded in bone and does not
contain luminal tissue (e.g. bowel, ureter, bile duct).

8. Ability to understand and the willingness to sign a written protocol specific informed
consent for tissue harvest or a parental/guardian informed consent and pediatric
assent when appropriate.

Tissue Procurement Exclusion Criteria:

1. Medical condition requiring any form of chronic systemic immunosuppressive therapy
(steroid or other) except physiologic replacement doses of hydrocortisone or
equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily)
for < 30 days duration.

2. Known history of other malignancy unless having undergone curative intent therapy
without evidence of that disease for ≥ 3 years except cutaneous squamous cell and
basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other
in situ cancers are allowed if definitively resected.

3. Brain metastases unless treated with curative intent (gamma knife or surgical
resection) and without evidence of progression for ≥ 2 months.

4. Any documented history of autoimmune disease with exception of Type 1 diabetes on
stable insulin regimen, hypothyroidism on stable dose of replacement thyroid
medication, vitiligo, or asthma not requiring systemic steroids.

5. Known HIV or chronic Hepatitis B or C infection.

6. Known hypersensitivity to any temozolomide component or to dacarbazine (DTIC).

7. Known hypersensitivity to irinotecan or its excipients.

8. Known history of allergies or sensitivities to gentamicin.

9. History of or current evidence of any condition (including medical, psychiatric or
substance abuse disorder), therapy, or laboratory abnormality that might confound the
results of the study, interfere with the patient's participation for the full duration
of the study, or is not in the best interest of the patient to participate, in the
opinion of the treating Investigator.

Study Enrollment Inclusion Criteria:

1. Completed manufacture of at least 4 vials of Vigil.

2. Karnofsky performance status (KPS) / Lansky performance status (LS) ≥80%.

3. Normal organ and marrow function as defined below:

Absolute granulocyte count ≥1,000/mm3, Absolute lymphocyte count ≥400/mm3, Platelets
≥75,000/mm3, Hemoglobin ≥ 8.0 mg/dL, Total bilirubin ≤ institutional upper limit of
normal*, AST(SGOT)/ALT(SGPT) ≤2x institutional upper limit of normal, Creatinine <1.5
mg/dL

* documented Gilbert's syndrome may be considered after medical monitor review

4. Subject has recovered to CTCAE Grade 1 (except for parameters noted in Item 3, above)
or better from all adverse events associated with prior therapy or surgery.
Pre-existing motor or sensory neurologic pathology or symptoms, or dermatologic must
be recovered to CTCAE Grade 2 or better.

5. If female of childbearing potential, has a negative urine or serum pregnancy test. If
the urine test is positive or cannot be confirmed as negative, a negative serum test
will be required for study entry.

6. Ability to understand and the willingness to sign a written informed protocol specific
consent or a parental/guardian informed consent and pediatric assent when appropriate.

Study Enrollment Exclusion Criteria:

In addition to the procurement exclusion criteria, subjects will NOT be eligible for study
registration and randomization if meeting any of the following additional criteria:

1. Any anti-neoplastic therapy between tissue procurement for Vigil manufacture and start
of study therapy.

2. Live vaccine used for the prevention of infectious disease administered < 30 days
prior to the start of study therapy.

3. Post-surgery complication that in the opinion of the treating investigator would
interfere with the patient's study participation or make it not in the best interest
of the patient to participate.