Study Drug Administration:
Each cycle is 21 days.
You will receive pembrolizumab by vein over about 30 minutes on Day 1 of each cycle. After
the first dose, you will stay in the clinic for an additional 60 minutes after the dose.
After that, if no intolerable side effects occur, you will only stay in the clinic for an
additional 30 minutes after each dose.
You will take 2 epacadostat pills by mouth every day while on study. Tablets should be taken
about 12 hours apart (1 morning dose, 1 evening dose) at the same time each day. Tablets
should be swallowed whole; do not chew, crush, dissolve, or divide the tablets. If you vomit
a dose of epacadostat, you may take a "make up" dose only if the tablets can be seen and
counted. If you miss a dose of epacadostat, you may take the tablets as soon as you remember
but only if it has not been more than 2 hours since your scheduled dose. If it has been more
than 2 hours, wait and take your next dose as scheduled.
You will be given a medication diary to keep track of when you take each dose of epacadostat.
The study staff will tell you when you should bring the diary and any unused tablets to the
Length of Study:
You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drugs if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.
Your participation in this study will be over after follow-up (described below).
On Day 1 of all cycles:
- You will have a physical exam.
- Blood (about 3 teaspoons) will be drawn for routine tests.
- During Cycles 1-5, blood (about 3 tablespoons) will be drawn for biomarker testing.
On Days 8 and 15 of Cycle 1, blood (about 3 tablespoons) will be drawn for biomarker testing.
Every 9 weeks for the first 36 weeks and then every 12 weeks after that, you will have an MRI
or CT scan.
If the disease appears to get worse, blood (about 3 tablespoons) will be drawn for biomarker
As soon as possible after your last dose of study drugs:
- You will have a physical exam.
- Blood (about 3 tablespoons) will be drawn for biomarker and routine tests.
If you stopped taking the study drugs for reasons other than the disease getting worse, you
will continue to have MRI or CT scans as described above.
About 30 days after your End-of-Treatment visit, blood (about 1 teaspoon) will be drawn to
check your thyroid function.
Long Term Follow-Up:
About every 8 weeks for the first 3 years and then every 12 weeks after that, a member of the
study staff will contact you to ask how you are doing. This contact will take place either
during a regularly scheduled clinic visit or by phone. Each phone call should last about 10
minutes. If the disease gets worse, you start a new cancer treatment, withdraw from the
study, or you cannot be reached, this contact will stop.
1. Be willing and able to provide written informed consent/assent for the trial.
2. Be >/= 18 years of age on day of signing informed consent.
3. Have received at least one prior therapy for metastatic disease.
4. Patients with HRD identified by one of the following criteria: a)Tested positive for
BRCA 1 or 2 germline deleterious mutation, b)Previously identified genetic aberrations
that are associated with HRD [e.g., somatic BRCA mutation, PALB2, Fanconi Anemia gene
or RAD51 mutations], c)Patients with somatic ATM loss as identifiable with
immunohistochemistry or with ATM mutation, d) PDAC patients with family history of 2
or more first-degree relatives with BRCA-associated cancers (stomach, breast, ovary)
or 1 or more first-degree relative with PDAC
5. Have measurable disease based on RECIST 1.1 or at least one site of disease must be
uni-dimensionally measurable as per RECIST 1.1. All radiology studies must be
performed within 28 days prior to registration
6. Patients must have an archival sample of tumor or metastatic site core biopsy to be
7. Have a performance status of 0 or 1 on the ECOG Performance Scale.
8. Demonstrate adequate organ function, all screening labs should be performed within 10
days of treatment initiation: a) Hematological: Absolute neutrophil count (ANC) >/=
1.5×109/L, platelet count >/= 100×109/L, and hemoglobin >/= 9 g/dl without transfusion
or EPO dependency (within 7 days of assessment). b) Renal: If serum creatinine
concentration >/= 1.5× upper limit of normal (ULN), then estimated creatinine
clearance must be >/= 60 mL/min for subject with creatinine levels > 1.5 ×
institutional ULN. c) Hepatic: total bilirubin </= 1.5× ULN (≤ 3 X ULN if a exists a
history of Gilbert syndrome alanine) or Direct bilirubin >/= ULN for subjects with
total bilirubin levels > 1.5 ULN, aminotransferase (ALT) and aspartate
aminotransferase (AST) </= 2.5× ULN and albumin >/= 3 mg/dL. Creatinine clearance
should be calculated per institutional standard.
9. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.
10. Female subjects of childbearing potential must be willing to use an adequate method of
contraception, for the course of the study through 120 days after the last dose of
study medication. Note: Abstinence is acceptable if this is the usual lifestyle and
preferred contraception for the subject.
11. Male subjects of childbearing potential must agree to use an adequate method of
contraception. Contraception, starting with the first dose of study therapy through
120 days after the last dose of study therapy. Note: Abstinence is acceptable if this
is the usual lifestyle and preferred contraception for the subject.
1. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment.
2. For screening ECGs, exclude patients with a QTcF > 480ms, or JTc > 340ms for those
with an intraventricular conduction delay. If the screening ECG has a QTcF > 480ms,
eligibility can be confirmed if the average of 3 ECGs done 5 minutes apart have an
average QTcF < 480 ms.
3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
4. Has a known history of active TB (Bacillus Tuberculosis)
5. Hypersensitivity to pembrolizumab or epacadostat or any of their excipients.
6. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., </= Grade 1 or at baseline) from adverse events
due to agents administered more than 4 weeks earlier.
7. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., </= Grade 1 or at
baseline) from adverse events due to a previously administered agent. Note: Subjects
with </= Grade 2 neuropathy are an exception to this criterion and may qualify for the
study. Note: If subject received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
8. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.
9. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging for at least four weeks
prior to the first dose of trial treatment and any neurologic symptoms have returned
to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis, which is excluded regardless of clinical stability.
10. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
11. Has a history of (non-infectious) pneumonitis that required steroids or current
12. Has an active infection requiring systemic therapy.
13. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
15. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.
16. Has received prior therapy with an anti-IDO-1 agent.
17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
19. Has received a live vaccine within 30 days of planned start of study therapy.
20. Has ascites that requires frequent paracentesis or a pleural effusion that requires
21. Has arterial vascular involvement.
22. Has received monoamine oxidase inhibitors within 21 days prior to starting study
23. Has any history of Serotonin Syndrome after receiving serotonergic drugs.