T Cell Immunotherapy for Advanced Ovarian Cancer

Treatment Part 1, All cohorts have leukapheresis.

Treatment Part 2, Cohort 1 Study Drug Administration:

If found to be eligible to take part in this study, participants will receive
cyclophosphamide by vein over about 30-60 minutes on Day -2 (2 days before they receive the
CD8+ T cells). If the doctor thinks it is needed, they will be given standard drugs to help
decrease the risk of side effects. They may ask the study staff for information about how the
drug is given and its risks.

On Day 0, they will receive the CD8+T cells by vein over about 30-60 minutes. They will stay
in the hospital overnight after the dose to monitor their condition. Starting within 6 hours
after the CD8+T cell infusion and then 2 times a day after that for 14 days, they will give
aldesleukin as an injection into their skin around abdomen. They will be taught how to give
themselves these injections. In order to reduce possible side effects they will take naproxen
sodium twice daily beginning the day before their injections and continuing for the 14 days.

All participants will receive the same dose level of cyclophosphamide, aldesleukin, and CD8+T
cells. Participants in this cohort will not receive utomilumab.

Study Visits:

On Day -2:

- They will have a physical exam.

- Blood (about 1 tablespoon) will be drawn for routine tests. This routine blood draw will
include a pregnancy test if they can become pregnant. To take part in this study, they
must not be pregnant.

On Day 0:

- They will have an EKG to check their heart function.

- They will a have physical exam before the infusion.

On Days 1, 7, 14, 22, 28, 35, 43, 49, 57, 64, 70, 77, 85, 113, and 141:

- They will have a physical exam.

- Blood (about 5½ tablespoons) will be drawn for routine tests, immune system tests, and
tests on how long the T-cells survive in their body.

- Between Day 35 and 42 and again between Day 77 and 84, they will have an MRI or CT scan
to check the status of the disease.

Treatment Part 2, Cohorts 2-3:

Study Drug Administration:

If found to be eligible to take part in this study, they will be assigned to a dose level of
utomilumab based on when they join study. Up to 3 dose levels of utomilumab will be tested.
The first group of participants will receive the lowest dose level. Each new group will
receive a higher dose than the group before it, if no intolerable side effects were seen.
This will continue until the highest tolerable dose of utomilumab is found.

All participants will receive the same dose level of cyclophosphamide, aldesleukin, and CD8+T
cells.

Because they are enrolled in Cohorts 2 and 3, they will receive cyclophosphamide by vein over
about 30-60 minutes on Day -2 (2 days before you receive the CD8+T cells).

On Day 0, they will receive the CD8+T cells by vein over about 30-60 minutes. They will stay
in the hospital overnight after the dose to monitor your condition. Starting within 6 hours
after the CD8+T cell infusion and then 2 times a day after that for 14 days, they will give
aldesleukin as an injection into their skin around their abdomen. They will be taught how to
give themselves these injections.

On Days 1, 29, 57, 85, 113, and 141, they will receive utomilumab by vein over about 90
minutes. Study Visits

On Day -2:

- They will have a physical exam.

- Blood (about 1 tablespoon) will be drawn for routine tests. This routine blood draw will
include a pregnancy test if they can become pregnant. To take part in this study, they
must not be pregnant.

On Day 0:

- They will have an EKG to check their heart function.

- They will have a physical exam before the infusion.

On Days 1, 7, 14, 22, 28, 35, 43, 49, 57, 64, 70, 77, 85, 113, and 141:

- They will have a physical exam.

- Blood (about 5½ tablespoons) will be drawn for routine tests, immune system tests, and
tests on how long the T-cells survive in their body.

- Between Day 35 and 42 and again between Day 77 and 84, they will have an MRI or CT scan
to check the status of the disease.

On Day 3, blood (about 5½ tablespoons) will be drawn for routine tests, immune system tests,
and tests on how long the T-cells survive in their body.

Inclusion Criteria:

1. Histopathologic documentation (must be performed or reviewed at MD Anderson) of
recurrent high grade epithelial ovarian cancer.

2. At least one prior line of platinum-based chemotherapy (subjects are eligible for
enrollment and leukopheresis while still platinum-sensitive, however, they must have
developed platinum resistant disease for treatment (turnstile 2)).

3. 18 to 75 years of age

4. Tumor expressing PRAME and/or COL6A3

5. Expression of HLA-A*0201

6. ECOG performance status of 0-1 and an expected survival of greater than 16 weeks.

7. Willing and able to give informed consent

8. Adequate normal organ and marrow function as defined below: Hemoglobin >/= 9.0 g/dL;
Absolute neutrophil count (ANC) >/= 1.0 x 10^9/L (> /=1000 per mm^3); Platelet count
>/= 75 x 10^9/L (>/=100,000 per mm^3); Serum bilirubin limit of normal (ULN) unless diagnosed with Gilbert's syndrome; AST and ALT ULN unless liver metastases are present, in which case it must be creatinine CL >40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection
for determination of creatinine clearance: Creatinine CL (mL/min) = [Weight (kg) x
(140 - Age) x 0.85]/[72 x serum creatinine (mg/dL)].

9. Subjects must either be of non-reproductive potential (ie, post-menopausal by history:
>/=50 years old and no menses for >/=1 year without an alternative medical cause; OR
history of hysterectomy, OR history of bilateral tubal ligation, OR history of
bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.

10. Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study in such a manner that the risk
of pregnancy is minimized. Suggested precautions should be used to minimize the risk
or pregnancy for at least 1 month before start of therapy, and while women are on
study for up to 3 months after T cell infusion, and at least 8 weeks after the study
drug is stopped

11. {Turnstile 2} Subjects must have platinum resistant disease (progression on a
platinum-containing regimen or recurrence within 180 days of last dose of
platinum-containing chemotherapy). Subjects that are not platinum resistant but are
deemed not to be candidates for platinum-based chemotherapy due to prior significant
allergic reaction may participate with PI approval.

12. {Turnstile 2} Bi-dimensionally measurable disease by radiographic imaging (MRI or CT
scan).

13. {Turnstile 2} At least 4 Weeks must have elapsed since the last chemotherapy,
immunotherapy, radiotherapy or major surgery. At least 6 Weeks for bevacizumab.

14. {Turnstile 2} Toxicity related to prior therapy must either have returned to 1, baseline, or been deemed irreversible.

Exclusion Criteria:

1. Clinically significant pulmonary dysfunction, as determined by medical history and
physical exam. Patients so identified will undergo pulmonary functions testing and
those with FEV1 < 60% of normal or DLco (corr for Hgb) < 55% will be excluded.

2. Significant cardiovascular abnormalities including any one of the following:
Congestive heart failure, Clinically significant hypotension, Symptoms of coronary
artery disease, Presence of cardiac arrhythmias on EKG requiring drug therapy; or
Patients with a history of cardiovascular disease. (Patients with the above will
undergo a cardiac evaluation which can include a stress test and/or echocardiography.
Results of this evaluation will be considered before excluding patients on the basis
of cardiovascular abnormalities). Subjects with evidence of stress-induced cardiac
ischemia or ejection fraction less than 55% will be excluded.

3. History of central nervous system (CNS) metastasis.

4. Autoimmune disease: Patients with a history of Inflammatory Bowel Disease are excluded
from this study, as are patients with a history of autoimmune disease (e.g. Systemic
Lupus Erythematosus, vasculitis, infiltrating lung disease) whose possible progression
during treatment would be considered by the Investigator to be unacceptable.

5. {Turnstile 2} Participation in another clinical study with an investigational product
administered during the last 28 days.

6. {Turnstile 2} Receipt of the last dose of previous chemotherapy, hormonal, or biologic
treatment for ovarian, fallopian tube, or primary peritoneal cancer in the last 28
days (in the last 6 weeks for bevacizumab).

7. {Turnstile 2} Current or prior use of immunosuppressive medication within 28 days
before enrollment, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid.

8. {Turnstile 2} Any prior Grade >/=3 immune-related adverse event (irAE) while receiving
any previous immunotherapy agent, or any unresolved irAE >Grade 1.

9. History of allogeneic organ transplant.

10. Unresolved partial or complete small or large bowel obstruction.

11. {Turnstile 2} Receipt of live attenuated vaccination within 30 days prior to
enrollment or within 30 days of planned lymphodepletion.

12. Any underlying medical or psychiatric condition, which in the opinion of the
Investigator, will make the administration of study drug hazardous or obscure the
interpretation of adverse events.

13. Active viral hepatitis

14. Confirmed HIV infection