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

Study Description

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Brief Summary:

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 systemic chemotherapy treatment regimens for advanced disease.

Condition or disease	Intervention/treatment	Phase
Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Esophageal Adenocarcinoma	Biological: CRS-207; Biological: Pembrolizumab	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	79 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 2, Open-label Evaluation of CRS-207 and Pembrolizumab in Adults With Recurrent or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinomas
Actual Study Start Date :	August 30, 2017
Estimated Primary Completion Date :	October 2018
Estimated Study Completion Date :	May 2019

Arms and Interventions

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Arm

Intervention/treatment

Experimental: CRS-207 and Pembrolizumab; Treatment cycle is once every 3 weeks. Pembrolizumab: 200 mg administered IV over 30 minutes on Day 1 of each 3 week cycle. CRS-207: starting dose 1×10^9 CFU administered IV over 1 hour on Day 2 of Cycle 1, on Day 1 of Cycles 2, 3, 4; and every 6 weeks thereafter. Treatment cycles will continue up to 24 months as long as there is adequate safety and potential for clinical benefit.

Biological: CRS-207; via IV infusion Biological: Pembrolizumab; via IV infusion; Other Name: MK-3475

Outcome Measures

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Primary Outcome Measures :

1. Number of patients with treatment-related adverse events as assessed by CTCAE v 4.0 [ Time Frame: Through study completion, an average of 18 months ]
   CTCAE = Common Terminology Criteria for Adverse Events

Secondary Outcome Measures :

1. Tumor response [ Time Frame: Through study completion, an average of 18 months ]
   RECIST (Response Evaluation Criteria in Solid Tumors) will be used to assess tumor response and progression
2. Survival [ Time Frame: From date of enrollment until the date of death or close of study, assessed at least 12 months from study completion ]
   Subjects will be observed for survival for at least 12 months from last dose of study drug
3. Characterization of immune responses [ Time Frame: From study start through study completion, an average of 18 months ]
   Peripheral blood will be collected to assess immune responses directed against Listeria monocytogenes, mesothelin and other tumor-associated antigens
4. Analysis of biomarker expression [ Time Frame: At screening (within 28 days of study start) and through study completion, an average of 19 months ]
   Tumor tissue samples will be used to analyze PD-L1 status and mesothelin status; phenotyping and characterization of tumor infiltrating lymphocytes and tumor microenvironment, functional genomic analyses and T cell receptor sequencing

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

   • Histologically-confirmed gastric or 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
5. Measurable/assessable disease, as defined by RECIST v1.1.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Can provide tissue for PD-L1 and mesothelin biomarker analysis

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 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.

Contacts and Locations

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Locations

United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
Mary Crowley Cancer Research
Dallas, Texas, United States, 75230
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101

Sponsors and Collaborators

Aduro Biotech, Inc.

Merck Sharp & Dohme Corp.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Aduro Biotech, Inc.
ClinicalTrials.gov Identifier:	NCT03122548 History of Changes
Other Study ID Numbers:	ADU-CL-14; KEYNOTE KN-463 ( Other Identifier: Merck Sharp & Dohme Corp. )
First Posted:	April 21, 2017
Last Update Posted:	February 15, 2018
Last Verified:	February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Aduro Biotech, Inc.:

stomach cancer; gastric cancer; esophageal cancer	digestive system diseases; gastrointestinal diseases; stomach diseases

Additional relevant MeSH terms:

Adenocarcinoma; Esophageal Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms	Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Pembrolizumab; Antineoplastic Agents