CD8+ T Cell Therapy and Pembrolizumab in Treating Patients With Metastatic Gastrointestinal Tumors

PRIMARY OBJECTIVES:

I. Assess the safety of using a personalized adoptive T cell therapy in patients with
advanced gastrointestinal malignancies.

SECONDARY OBJECTIVES:

I. Assess the persistence of an immune response after T cell infusion. II. Determine the
clinical benefit of adoptive T cell therapy in advanced gastrointestinal cancers.

OUTLINE:

Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide
intravenously (IV) over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on
day 0 and receive aldesleukin subcutaneously (SC) twice daily (BID) on days 1-14. Beginning
on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over
30-60 minutes on weeks 3, 6, 12, and 15.

After completion of study treatment, patients are followed up for 24 weeks.

Inclusion Criteria:

1. Histopathologic documentation of pancreatic adenocarcinoma, colorectal adenocarcinoma,
cholangiocarcinoma, esophageal cancer and gastric cancer with radiographic evidence of
metastatic disease.

2. Male or female subjects greater than or equal to 18 years of age.

3. ECOG/ Zubrod performance status of 0 or 1.

4. 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 at least 8 weeks after pembrolizumab is stopped. WOCBP include any female
who has experienced menarche and who has not undergone successful surgical
sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is
not postmenopausal. Acceptable forms of birth control include condom, diaphragm,
hormonal, IUD, or sponge plus spermicide. Abstinence is also an acceptable form of
birth control.

5. Men must be willing and able to use an acceptable method of birth control, during and
for at least 3 months after completion of the study, if their sexual partners are
WOCBP.

6. Willing and able to give informed consent.

7. Adequate vein access: consider PICC or other central line.

8. Patients must have adequate tissue (fresh or frozen) available or planned removal of
adequate tissue for analysis. At least 250mg of tumor are needed for peptide elution.
There is no specific time limit on how long the tissue can remain frozen prior to use.
The tissue will be collected and analyzed under Lab protocol PA15-0176.

9. Patients can have any lines (including zero) of prior therapy to sign consent prior to
tissue harvest.

10. Toxicity related to prior therapy must either have returned to or been deemed irreversible.

11. ELIGIBILITY FOR TREATMENT: ECOG/Zubrod performance status of 0 to 2.

12. Bi-dimensionally measurable disease by radiographic imaging (CT scan) that represents
at least one measurable lesion per RECIST v1.1.

13. At least 4 Weeks must have elapsed since the last chemotherapy, radiotherapy or major
surgery.

14. Toxicity related to prior therapy must either have returned to less than or equal to
grade 1, baseline, or been deemed irreversible.

15. Subjects must have received at least one line of chemotherapy prior to receiving
adoptive T cell therapy and should have exhausted standard of care systemic therapy
options. The decision to implement the T cell therapy will be at the discretion of the
treating physician. The timing and total exposure to chemotherapy will depend on the
tumor type in question (more systemic options for breast cancer; fewer for gastric
cancer, for example). Due to the heterogeneity of tumors being treated in this
protocol, the discretion of the treating physician in terms of timing of immunotherapy
will be critical.

Exclusion Criteria:

1. EXCLUSION FOR ENROLLMENT: Any other malignancy from which the patient has been
disease-free for less than 5 years, with the exception of adequately treated and cured
basal or squamous cell skin cancer, superficial bladder cancer, and carcinoma in situ
of the cervix.

2. Pregnant women, nursing mothers, men or women of reproductive ability who are
unwilling to use effective contraception. Women of childbearing potential with a
positive pregnancy test within 3 days prior to entry.

3. Significant cardiovascular abnormalities as defined by any one of the following: 1.
Congestive heart failure NYHA classes II-IV. Patients with asymptomatic class I CHF
may participate in conjunction with a Cardiology consultation. 2. Clinically
significant hypotension. 3. Symptoms of coronary artery disease. 4. Presence of
arrhythmias in EKG requiring drug therapy.

4. Active and untreated central nervous system (CNS) metastases (including metastasis
identified during screening MRI or contrast CT). Patients with asymptomatic, treated
metastases may be eligible if their lesion(s) have demonstrated stability over 2
months.

5. 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.

6. 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, such as a condition associated with frequent
diarrhea.

7. Inadequate organ function at enrollment defined by: WBC less than or equal to 2000/uL.
Hct less than or equal to 24% or Hgb less than or equal to 8 g/dL. ANC less than or
equal to 1000. Platelets less than or equal to 75,000. Creatinine greater than or
equal to 1.5 x ULN OR creatinine clearance >50 ml/min/1.73m2 for patients with
creatinine levels above institutional normal limits. AST/ALT greater than or equal to
2.5 x ULN. Bilirubin greater than or equal to 2.0 x ULN

8. Positive screening tests for HIV, Hep B, and Hep C. If positive results are not
indicative of true active or chronic infection, the patient can be treated

9. EXCLUSION CRITERIA FOR TREATMENT: WBC less than or equal to 2000/uL. Hct less than or
equal to 24% or Hgb less than or equal to 8 g/dL. ANC less than or equal to 1000.
Platelets less than or equal to 75,000. Creatinine greater than or equal to 1.5 x ULN
OR creatinine clearance >50 ml/min/1.73m2 for patients with creatinine levels above
institutional normal limits. AST/ALT greater than or equal to 2.5 x ULN. Bilirubin
greater than or equal to 2.0 x ULN

10. Pregnant women, nursing mothers, men or women of reproductive ability who are
unwilling to use effective contraception. Women of childbearing potential with a
positive pregnancy test within 3 days prior to entry.

11. Steroids are not permitted 3 days prior to T cell infusion and concurrently during
therapy.

12. Uncontrolled concurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

13. Any non-oncology vaccine therapy used for the prevention of infectious disease within
1 month before or after any anti-PD-1 dose.

14. After the T cell infusion, patients may not be on any other treatments for their
cancer aside from those included in the treatment section of the protocol.

15. Coagulation ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long
as PT or a PTT is within therapeutic range of intended use of anticoagulants.