Peptide Vaccine in Advanced Pancreatic Ductal Adenocarcinoma or Colorectal Adenocarcinoma

Tissue Collection:

Within 4 weeks after signing this informed consent document, as part of the screening tests:

°You will have leftover frozen tissue collected to create your vaccine, if available. If
there is not enough frozen tissue available, then leftover tissue from a recent procedure
performed as part of your standard of care will be collected. The study staff may ask you to
take part in another MD Anderson clinical research study (PA15-0176) for collection of
leftover tissue. The study doctor will discuss this with you and, if you decide to take part,
you will sign a separate informed consent document.

After the tissue cells have been collected, your vaccine will be made.

The vaccine can also be made from blood cells. If you agree, you will be consented and
enrolled under a separate protocol, PA14-0138, to have the leukapheresis procedure performed.
Leukapheresis is a special type of blood draw procedure that separates the red blood cells,
white blood cells, and other parts of your blood from each other. The consent form for this
protocol will explain how the leukapheresis procedure is performed and its risks. The white
blood cells collected from leukapheresis will be used in this study.

Baseline Tests:

You must receive at least 1 type of chemotherapy after you are enrolled in this study but
before your first dose of vaccine. There is no limit to the number of types of chemotherapy
you may receive. Your study doctor will decide when you will enter the treatment part of this
study.

Within 28 days after your last dose of chemotherapy:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests. The routine blood draw will
include a pregnancy test if you can become pregnant.

Within 14 days before your first dose of vaccine, you will have an MRI or CT scan of the
chest, abdomen, and pelvis.

Study Vaccine and Study Drug Administration:

About 28 days after your last dose of chemotherapy, you will receive the vaccine as an
injection under the skin on Day 1 of Weeks 0, 1, 3, 4, 6 and then every 3 weeks until Week
30, then at Weeks 39 and 51.

Imiquimod cream will be applied over the injection site about 30 minutes after you receive
the vaccine. This will be done each time you receive the vaccine.

You will also receive pembrolizumab by vein over about 30 minutes every 3 weeks until Week
51.

Study Visits:

On Day 1 of Weeks 0, 1, and 3:

- You will have a physical exam.

- Blood (about 6 tablespoons) will be drawn for routine tests and research tests for
immune testing to test for genetic mutations.

On Day 1 of Week 4, blood (about 6 tablespoons) will be drawn for immune system testing and
routine tests.

On Day 1 of Weeks 6, 9, 12, 15, and 18:

- You will have a physical exam.

- Blood (about 6 tablespoons) will be drawn for immune system testing and routine tests.

- You will have an MRI or CT scan of the chest, abdomen, and pelvis. You will not have
these scans at Weeks 9 and 15.

On Day 1 of Weeks 16, 21, 24, 27, 33, 36, 42, 45, and 48:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

On Day 1 of Weeks 30, 39, and 51:

- You will have a physical exam.

- Blood (about 6 tablespoons) will be drawn for immune system testing, tumor marker
testing, and routine tests.

- You will have an MRI or CT scan of the chest, abdomen, and pelvis.

Length of Study:

You may receive the vaccine and pembrolizumab for up to 1 year.

You will no longer be able to receive the study vaccine if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after follow-up.

End-of-Study Visit:

About 8 weeks after your last study visit:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

Follow-Up:

You will be called 2 times by the study staff in the 6 months after your last dose of vaccine
and asked about any side effects you may have experienced since the end-of-study visit. Each
call should last about 10 minutes.

If you left the study because you had side effects, you will be called by the study staff
until that side effect has gone away or has become stable.

Inclusion Criteria:

1. Patients must have metastatic Pancreatic Ductal Adenocarcinoma (PDA) or metastatic
colorectal cancer (CRC) to be eligible. (PDA patients with an elevated tumor marker
following a primary pancreatic surgery would be eligible).

2. Patients can have any lines (including zero) of prior therapy to sign consent prior to
tissue harvest. Vaccination will not take place until at least one line of standard
chemotherapy is given.

3. Patients must have adequate fresh or frozen tissue available. If tissue is needed,
then subjects may have had it previously collected under protocol PA15-0176.

4. Age =/>18 years.

5. ECOG performance status <1 (Karnofsky >70%)

6. Life expectancy of greater than 6 months.

7. Patients must have normal organ and marrow function as defined below:: a) leukocytes
=/>3,000/mcL; b) absolute neutrophil count =/>1,000/mcL; c) platelets =/>75,000/mcL;
d)total bilirubin =/< 2.0 X institutional upper limit of normal; e)
AST(SGOT)/ALT(SGPT) =/<2.5 X institutional upper limit of normal (except in gilberts
disease where direct bilirubin will be used); f) calculated creatinine clearance =/>50
mL/min/1.73 m^2

8. Patients must demonstrate an ability to understand and the willingness to sign a
written informed consent document.

9. The effects of a peptide based vaccine on the developing human fetus are unknown. For
this reason, women of child-bearing potential and men must agree to use adequate The
effects of a peptide based vaccine on the developing human fetus are unknown. For this
reason, women of child-bearing potential and men must agree to use adequate
contraception at study entry and for the duration of study participation. Should a
woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately. Birth control specifications:
unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s),
sexually active participants must use birth control during and for >120 days after the
study. Abstinence is also an acceptable form of birth control.

10. Inclusion criteria just prior to first vaccination (within 21 days) in addition to
above inclusion criteria unless specified differently below : ECOG performance status
=/<2 (Karnofsky =/>60%)

11. Inclusion criteria just prior to first vaccination (within 21 days): Life expectancy
of greater than 4 months

12. Inclusion criteria just prior to first vaccination (within 21 days): Patients must
have either measurable disease per RECIST v1.1 or evaluable disease defined as an
elevated tumor biomarker (CA19-9, CEA or cfDNA mutation). Pancreatic cancer patients
with an elevated tumor marker following a primary pancreatic surgery would be eligible

Exclusion Criteria:

1. Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS).HIV-positive patients on combination
antiretroviral therapy are ineligible because of the potential for lack of efficacy of
therapeutic cancer vaccine.

2. Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events.

3. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus
(ribonucleic acid or HCV antibody) indicating acute or chronic infection.

4. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
requiring hormone replacement, psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted
to enroll.

5. Subjects with a condition requiring systemic treatment with either corticosteroids (>
10 mg daily prednisone equivalents) or other immunosuppressive medications. Inhaled or
topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents
are permitted in the absence of active autoimmune disease.

6. 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.

7. Women of child bearing potential who are pregnant or breastfeeding. Women with a
positive pregnancy test at enrollment or prior to administration of vaccine.

8. Has history of (non-infectious) pneumonitis that required steroids, evidence of
interstitial lung disease or active, non-infectious pneumonitis

9. Known history of active TB (Bacillus Tuberculosis)

10. Hypersensitivity to pembrolizumab or any of its excipients.

11. Has a known additional malignancy that is progressing or requires active treatment.

12. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

13. Exclusion criteria just prior to first vaccination - (within 21 days) - in addition to
above exclusion criteria unless specified differently below: Patients who have had
chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who
have not recovered to baseline from adverse events due to agents administered more
than 2 weeks earlier (washout period).

14. Exclusion criteria just prior to first vaccination- (within 21 days) - in addition to
above exclusion criteria unless specified differently below: Women of child bearing
potential who are pregnant or breastfeeding. Women with a positive pregnancy test
prior to administration of vaccine.

15. Exclusion criteria just prior to first vaccination - (within 21 days) - in addition to
above exclusion criteria unless specified differently below: 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.

16. Exclusion criteria just prior to first vaccination - (within 21 days) - in addition to
above exclusion criteria unless specified differently below: Patients may not be
receiving any other investigational agents.

17. Exclusion criteria just prior to first vaccination - (within 21 days) - in addition to
above exclusion criteria unless specified differently below: Has received a live
vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza
vaccines for injection are generally inactivated flu vaccines and are allowed; however
intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are
not allowed.