Safety and Efficacy of CRS-207 With Pembrolizumab in Gastric, Gastroesophageal Junction or Esophageal Cancers

A Phase 2, Open-label Evaluation of CRS-207 and Pembrolizumab in Adults With Recurrent or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinomas

The purpose of this study is to determine whether CRS-207 in combination with pembrolizumab is safe and effective in adults with recurrent or metastatic gastric, gastroesophageal junction, or esophageal cancer who have received one or two prior chemotherapy regimens for advanced disease.

Inclusion Criteria:

1. Diagnosis with confirmed histology of one or more of the following:

   • Histologically-confirmed gastric or gastroesophageal junction (GEJ) adenocarcinoma (Siewert type II/III classification), or
   • Histologically-confirmed inoperable superior, medial, or distal third esophageal adenocarcinoma (Siewert type I classification may be included, provided there is no mixed histology)

2. Confirmed recurrent or metastatic disease

3. Received and experienced disease progression on, or following one or two prior chemotherapy regimens for advanced disease.

4. HER-2/neu negative or, if HER-2/neu positive, disease must have previously progressed on treatment with trastuzumab; prior treatment must have included a platinum and a fluoropyrimidine.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

6. Can provide tissue for PD-L1 and mesothelin biomarker analysis

7. Adequate organ and marrow function at screening

Exclusion Criteria:

1. Diagnosis of squamous or undifferentiated gastric cancer
2. Individuals with inaccessible tumors or for whom biopsy is contraindicated
3. Participated in any other study in which receipt of an investigational new drug or investigational device occurred within 28 days of first dose of study drug
4. Receiving tumor necrosis factor (TNF) pathway inhibitors, PI3 kinase inhibitors, systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
5. Clinical evidence of ascites by physical exam
6. Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug or has not recovered from adverse effects due to agents administered more than 4 weeks earlier
7. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study drug, or has not recovered from adverse effects due to a previously-administered agent
8. Subjects who have implanted medical devices that pose high risks for colonization and cannot be easily removed (e.g. artificial heart valves, pacemakers, prosthetic joints, orthopedic screw(s), metal plate(s)) if infection occurs. Other common devices such as venous access devices (e.g. Port-a-Cath or Mediport) may be permitted as well as arterial and venous stents and dental and breast implants that were placed more than 3 months prior to first dose of study drug.