Study of Pembrolizumab in Subjects With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Who Progressed After First-Line Therapy With Platinum and Fluoropyrimidine: Integration of Molecular Subtypes Through Integrative Genomic Analysis
Condition: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
MeSH terms: Adenocarcinoma; Esophageal Neoplasms
Intervention: pembrolizumab
Intervention description: 200 mg every 3 weeks
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No

Summary:

      This is a single-arm, single-center, open-label trial of pembrolizumab (MK-3475) in subjects
      with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who have progressed
      after failure of any combination chemotherapy containing a platinum and a fluoropyrimidine
      agent.

      Approximately 60 subjects will be enrollment to evaluate the efficacy and safety of
      pembrolizumab.

      Enrollment will begin with all subjects without regard for PD-L1 expression status. An
      evaluable specimen for PD-L1 status must be available and confirmed prior to enrollment.

      All study subjects will be evaluated every 6 weeks (+/- 7 days) following the date of IP drug
      adminstration for the first six months and every 12 weeks (+/- 7 days) thereafter until
      progression of disease is documented with radiologic imaging (computed tomography or magnetic
      resonance imaging).

      In the expansion cohort (cohort B), it was expanded on the original cohort based on response
      analysis and will be opened separately.

      Of the 5 MSI-high patients who were enrolled on to original cohort, all 5 MSI high GC
      patients (100% response rate) demonstrated dramatic response rate.

      Based on this finding, in order to proven Pembrolizumab's efficacy to specific MSI-H GC
      population, we would like enroll 20 more patients in cohort B. Based on our screening
      protocol, the prevalence of MSI-high in GC is about 15 %. Only MSI-high GC patients will be
      included. All the eligibility will be the same.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be willing and able to provide written informed consent/assent for the trial. The
             subject may also provide consent for Biomedical Research. However, the subject may
             participate in the main trial without participating in Biomedical Research.

          2. Be 19 years of age on day of signing informed consent

          3. Have histologically or cytologically-confirmed diagnosis of gastric or
             Gastroesophageal Junction Adenocarcinoma

          4. Have metastatic disease or locally advanced, unresectable disease.

          5. Has experienced documented objective radiographic or clinical disease progression
             during or after first-line therapy containing any platinum,fluoropyrimidine doublet.

          6. Have measurable disease based on RECIST as determined by investigator. Tumor lesions
             situated in a previously irradiated area are considered measurable if progression has
             been demonstrated in such lesions.

          7. Be willing to provide fresh tissue for biomarker analysis, and, based on the adequacy
             of the tissue sample quality for assessment of biomarker status. Repeat samples may be
             required if adequate tissue is not provided. Newly obtained endoscopic biopsy
             specimens are preferred to archived samples and formalin-fixed, paraffin-embedded
             block specimens are preferred to slides.

          8. Have a performance status of 0 or 1 on the ECOG Performance Scale.

          9. Demonstrate adequate organ function, all screening labs should be performed within 10
             days of treatment initiation.

         10. 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.

         11. Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication. Subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year.

         12. Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study therapy.

         13. (Only Cohort B) confirmed as MSI-H via the PCR or IHC staining by institutional
             standard.

        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 squamous cell or undifferentiated gastric cancer.

          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
             treatment.

          4. Has a known history of active Bacillus Tuberculosis

          5. Hypersensitivity to pembrolizumab or any of its excipients.

          6. Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or
             who has not recovered 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 from adverse events due
             to a previously administered agent.

          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 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. Replacement therapy is not considered a form of systemic treatment.

         11. Has known history of, or any evidence of active, non-infectious pneumonitis.

         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-PD-1, anti-PD-L1, or anti-PD-L2 agent.

         17. Has a known history of Human Immunodeficiency Virus

         18. Has known active Hepatitis B or Hepatitis C

         19. Has received a live vaccine within 30 days of planned start of study therapy.

         20. Is or has an immediate family member who is investigational site or 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.