Gastric cancer is one of the most common cancers worldwide. Surgical resection is the primary
treatment for gastric cancer but most patients present with locally advanced disease and
recurrence is common after surgery. Many patients (35%) will have early recurrence within 6-9
months of surgery indicating the need for more aggressive upfront therapy in these subjects.
In addition, the majority of patients will ultimately have recurrence and 5 year survival
rates are 35-40% despite aggressive therapy.
The ability to combine immunotherapy with pembrolizumab gives the potential to increase
therapeutic options while continuing standard of care chemotherapy. The particular use of
maintenance therapy may delay or eliminate the growth of residual micrometastatic disease and
lead to durable disease control. Additionally, this study provides the foundation for
substantial correlative work to define tumor and patient characteristics that may predict for
response to pembrolizumab in gastric cancer.
Inclusion Criteria:
1. Have previously untreated localized gastric or GE junction adenocarcinoma as defined
by T2 or greater primary lesion or the presence of any positive nodes- N+(clinical
nodes) without evidence of metastatic disease.
2. Plan to proceed to surgery following peri-operative chemotherapy based on standard
staging studies per local practice.
3. Be willing and able to provide written informed consent/assent for the trial. The
subject may also provide consent for Future Biomedical Research. However, the subject
may participate in the main trial without participating in Future Biomedical Research.
4. Be at least 18 years of age on day of signing informed consent.
5. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
prior to initiation of treatment on Day 1.
6. Have a performance status of 0 or 1 on the ECOG Performance Scale.
7. Demonstrate adequate organ function as defined below, all screening labs should be
performed within 14 days of treatment initiation.
Adequate Organ Function Laboratory Values
- Absolute neutrophil count (ANC) ≥1,500 /mcL
- Platelets ≥100,000 / mcL
- Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7
days of assessment)
- Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be
used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60
mL/min for subject with creatinine levels > 1.5 X institutional ULN
- Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with
total bilirubin levels > 1.5 ULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver
metastases
- Albumin >2.5 mg/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless
subject is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
of intended use of anticoagulants
- Creatinine clearance should be calculated per institutional standard.
8. Have a 2D Echocardiogram with left ventricular ejection fraction = or > 45% in order
to receive Epirubicin. Subjects with inadequate EF or other contraindication can
proceed on study without the use of Epirubicin.
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 - 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.
Exclusion Criteria:
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. 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
treatment. The use of physiologic doses of corticosteroids (prednisone 10 mf or
equivalent) may be approved after consultation.
3. Has a known history of active TB (Bacillus Tuberculosis)
4. Hypersensitivity to pembrolizumab or any of its excipients.
5. Has had any prior chemotherapy, targeted small molecule therapy, or radiation therapy
for their current diagnosis.
6. Has a known additional malignancy that is progressing or requires active treatment
within 3 years from registration. 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. Subjects with a history of prior malignancy diagnosed and
treated greater than 3 years form registration may be considered with consultation of
the primary investigator.
7. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis.
8. 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.
9. Has known history of prior pneumonitis requiring treatment with steroids, or any
evidence of active, non-infectious pneumonitis.
10. Has an active infection requiring systemic therapy which is not expected to have
resolved by Cycle 1 Day 1 dosing.
11. Has a history or current evidence of any condition (e.g. known deficiency of the
enzyme dihydropyrimidine dehydrogenase [DPD]),, 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.
12. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
13. 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.
14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
17. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or
child) who is investigational site or sponsor-investigator staff directly involved
with this trial, unless prospective IRB approval (by chair or designee) is given
allowing exception to this criterion for a specific subject.
18. 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.
