This is an expanded access study involving an investigational product named Vigil. Vigilis considered immunotherapy. Patients who participated in another clinical trialsponsored by Gradalis, and had Vigil made from their tumor tissue removed from a standardoperation, however failed the criteria to enroll in the other clinical trial to receiveVigil are eligible to screen for this expanded access trial to receive the Vigil madefrom their cancer cells.In this study, eligible participants will receive intradermal (under the skin) injectionsof Vigil, once every 4 weeks (28 days) for 1-12 doses, depending on the number of dosesthat was made from the cancer cells and if the participant is clinically stable. Duringthe treatment portion of the study, in addition to receiving Vigil injections,participants will also have a physical exam, blood collection for routine and researchtests, and assessment of medications, adverse events, and performance status informationwill be collected. Radiological tumor assessments will be performed every 3 months fromCycle 1. Once treatment ends, participants will continue to be seen in the clinic every 3months for similar assessments until disease progression occurs. After diseaseprogression, participants will be contacted by phone 4 times a year to determine poststudy treatment and survival status information.
This is an Expanded Access trial of Vigil (bi-shRNAfurin and GMCSF Augmented Autologous
Tumor Cell Immunotherapy) in Advanced Solid Tumors. Approximately 40 subjects who had
tissue procured and Vigil manufactured but fail manufacturing release criteria under a
previous Gradalis protocol are considered for this study.
Eligible participants will receive a minimum of 1 and a maximum of 12 doses of Vigil
intradermal injections every 4 weeks as monotherapy. Participants will be managed in an
outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes
will be monitored. Blood for immune function analyses in response to autologous tumor
antigens will be collected at screening, Day 1 (prior to Vigil administration) at Cycles
2, 4, and 6, end of treatment (EOT); 3 months after EOT, and every 6 months thereafter
for those in response follow up. For subjects with Ewing's sarcoma, blood for ctDNA
analysis will be collected at screening, on Day 1 prior to Vigil administration at Cycles
2, 3, 4, and 6, and EOT.
Biological: Vigil
Vigil is composed of autologous tumor cells harvested from the patient at the time of
initial de-bulking surgery which are then transfected extracorporeally, with a plasmid
encoding for the gene for GM-CSF, an immune-stimulatory cytokine, and a bifunctional,
short hairpin RNA which specifically knocks down the expression of furin, the critical
convertase responsible for production of the two TGβ isoforms (TGFβ-1 and TGFβ-2).
Other Name: Engineered Autologous Tumor Cell Immunotherapy,FANG,IND 14205
Study Enrollment Inclusion Criteria:
1. Histologically confirmed advanced or metastatic non-curable solid tumor.
2. Completed manufacture of at least 1 vial of Vigil, but failure of one or more
manufacturing release criteria.
3. ECOG performance status (PS) 0-1 or Karnofsky performance status (KPS) / Lansky
performance status (LS)≥ 70%.
4. 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
5. No systemic therapy, immunologic therapy or investigational therapy within 2 weeks
and no radiation therapy within 1 week prior to enrollment.
6. Subject has recovered to CTCAE Grade 1 (except for parameters noted in Item 4,
above) or better from all adverse events associated with prior therapy or surgery.
Pre-existing motor, sensory neurologic pathology or symptoms, or dermatologic
toxicities must be recovered to CTCAE Grade 2 or better.
7. 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.
8. 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:
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. Receipt of greater than 2 lines of systemic treatment between Vigil manufacture and
screening for this protocol.
4. Live vaccine used for the prevention of infectious disease administered < 30 days
prior to the start of study therapy.
5. Post-surgery complication that in the opinion of the treating investigator would
interfere with the subject's study participation or make it not in the best interest
of the patient to participate.
6. Brain metastases unless treated with curative intent (gamma knife or surgical
resection) and without evidence of progression for ≥ 2 months.
7. 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.
8. Known HIV or chronic Hepatitis B or C infection.
9. Known history of allergies or sensitivities to gentamicin.
10. 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.
Texas Oncology - Pediatrics
Dallas, Texas, United States
John Nemunaitis, MD, Study Director
Gradalis, Inc.