Trial of Atezolizumab and Vigil for Advanced Gynecological Cancers (A Companion Study to CL-PTL-119)

This is a randomized, open label intra-patient crossover study of Vigil, the checkpoint
inhibitor Atezolizumab and the combination of the two agents, in patients with epithelial
ovarian cancer, or other gynecological cancers (i.e., cervical, uterine). Eligible patients
will be randomized to receive two cycles of Vigil alone or two cycles of Atezolizumab alone,
followed by combination treatment with the two agents. Patients may continue on single agent
Atezolizumab until disease progression, only if pre-approved by Sponsor.

This study is intended as a companion study to protocol CL-PTL-119, A Randomized, Double
Blind, Placebo Controlled Phase 2 trial of Vigil Engineered Autologous Tumor Cell
Immunotherapy in Subjects with Stage IIIb-IV Ovarian Cancer in Clinical Complete Response
following Surgery and Primary Chemotherapy, otherwise known as the VITAL study. Patients who
have tumor harvested at surgery and Vigil successfully manufactured, but then are ineligible
for randomization onto the VITAL study or previously randomized to placebo, and also in
patients who have recurrent ovarian cancer will be offered the opportunity to participate in
this protocol.

Subjects enrolled will either be:

- Patients with recurrent ovarian disease. Furthermore, subjects who have previously
received Vigil on this study may be considered for re-procurement for manufacture of
Vigil (after consultation and approval from Sponsor) and re-enrolled into Part 2, OR

- Patients with ovarian cancer who failed to meet the eligibility criteria for Protocol
CL-PTL-119 because of failure to achieve a complete clinical response following primary
debulking surgery and standard paclitaxel/carboplatin therapy, OR

- Patients who failed to meet the eligibility criteria for Protocol CL-PTL-119 because of
a histologic diagnosis of another gynecological cancer (i.e., cervical, uterine) and not
ovarian cancer, OR

- Patients who were randomized on Protocol CL-PTL 119 and were subsequently unblinded at
recurrence and were assigned to the placebo arm.

Tissue Procurement Inclusion Criteria:

Subjects will be eligible for tissue procurement for the Vigil manufacturing process, if
they meet all of the following criteria:

1. Histologically confirmed Stage IIIb, IIIc or IV high-grade papillary serous, clear
cell, or endometrioid ovarian, fallopian tube or primary peritoneal carcinoma

2. Age ≥ 18 years.

3. Estimated survival ≥ 6 months.

4. ECOG Performance Status ≤ 1

5. Metastatic disease

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) or ascites fluid estimated volume
≥ 500mL (from a primary or secondary paracentesis, 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 informed protocol specific
consent for tissue harvest or a parental/guardian informed consent and pediatric
assent when appropriate.

Tissue Procurement Exclusion Criteria:

Subjects meeting any of the following criteria are not eligible for tissue procurement for
the Vigil manufacturing:

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 history of allergies or sensitivities to gentamicin.

7. 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.

8. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
antibodies, other investigational agent) less than 21 days prior to tissue
procurement.

Study Enrollment Inclusion Criteria:

Subjects will be eligible for registration into the trial if they meet all of the following
inclusion criteria:

1. Successful manufacturing of at least 4 vials of Vigil.

2. One of the following:

1. Failure to meet the eligibililty criteria for Protocol CL-PTL-119 due to i)
histology of ovarian cancer and failure to achieve a complete clinical response
following primary debulking surgery and standard paclitaxel/carboplatin therapy
OR, ii) a histologic diagnosis of another gynecologic malignancy which is not
ovarian cancer.

2. Recurrent ovarian cancer.

3. Randomized on Protocol CL-PTL-119 and were subsequently unblinded at recurrence
and were assigned to the placebo arm.

3. ECOG performance status (PS) ≤ 1 (or ≤ 2 due to carcinoid syndrome).

4. Estimated survival ≥ 6 months.

5. Measureable per RECIST 1.1 or evaluable disease.

6. Adequate organ and bone marrow function as defined below:

1. Absolute neutrophil count (ANC) ≥ 1.5 × 10e9/L (1500 per mm^3)

2. Platelets >100 × 10e9/L (100,000 per mm^3)

3. Hemoglobin ≥9.0 g/dL (5.59 mmol/L)

4. Creatinine clearance (CrCL) >50 mL/min by the Cockcroft-Gault formula or by
24-hour urine collection for determination of creatinine clearance:

Females:

CrCL (mL/min) = Weight (kg) × (140 - Age) × 0.85/72 × serum creatinine (mg/dL)

5. Serum bilirubin ≤1.5 × upper limit of normal (ULN). This will not apply to
patients with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of evidence
of hemolysis or hepatic pathology) who will be allowed in consultation with their
physician.

6. AST and ALT ≤2.5 × ULN in patients with no liver metastasis

7. AST or ALT ≤5 × ULN in patients with liver metastasis

8. TSH within institutional limits. If TSH is greater or less than institutional
limits patients may participate if their T4 is within normal limits (WNL);
patients may be on a stable dose of replacement thyroid medication; dose
adjustments are allowed if needed

7. Subject has recovered to CTCAE Grade 1 or better from all adverse events associated
with prior therapy or surgery (or ≤ 2 due to carcinoid syndrome).

8. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to
CTCAE Grade 2 or better

9. Patients with irreversible toxicity that is not reasonably expected to be exacerbated
by the IPs (Vigil and/or atezolizumab) may be included (e.g., hearing loss) after
consultation with the Principal Investigator

10. Subjects who are not rendered surgically sterile as a result of surgery for ovarian
cancer, must have, 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.

11. Ability to understand and the willingness to sign a written informed protocol specific
consent.

12. Willing and able to comply with the protocol for the duration of the study including
undergoing treatment and scheduled visits and examinations including follow up.
Patients must have fully recovered from chemotherapy associated toxicities prior to
starting treatment on this protocol.

13. Palliative radiotherapy is permitted provided:

1. More than 3 weeks have elapsed between the end of radiotherapy and the first dose
of study therapy, AND

2. The irradiated lesion(s) (unless measurable progression after irradiation) cannot
be used as target lesions.

Study Enrollment Exclusion Criteria:

In addition to the procurement exclusion, subjects (both with Vigil manufactured and
undergoing procurement) will NOT be eligible for study registration and enrollment if
meeting any of the following criteria:

1. Participation in another clinical study with an investigational product within the
last 3 weeks prior to study start.

2. Receipt of steroid therapy within the 2 weeks of the first dose of study therapy.

3. Live vaccine used for the prevention of infectious disease administered < 30 days
prior to the start of study therapy. NOTE: Subjects, if enrolled, should not receive
live vaccine during the study and for 5 months after the last dose of atezolizumab.

4. 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 subject to participate.

5. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3
electrocardiograms (ECGs) using Fridericia's Correction.

6. Female subjects who are pregnant, breast-feeding or of reproductive potential who are
not employing an effective method of birth control defined in the protocol. Effective
contraception is required for women receiving atezolizumab for 5 months after the last
dose.

7. Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results.

8. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
antibodies, other investigational agent) less than 21 days prior to the first dose of
study drug or less than 6 weeks for nitrosourea or mitomycin C.

9. Receipt of any anti-cancer therapy between tissue procurement on CL-PTL-126 and first
dose of study drug.