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

Primary Purpose

Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CRS-207
Pembrolizumab
Sponsored by
Aduro Biotech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Adenocarcinoma focused on measuring stomach cancer, gastric cancer, esophageal cancer, digestive system diseases, gastrointestinal diseases, stomach diseases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UCLA Medical Center
  • University of Colorado
  • University of Chicago Medical Center
  • Johns Hopkins University
  • Henry Ford Hospital
  • Memorial Sloan Kettering Cancer Center
  • Mary Crowley Cancer Research
  • Virginia Mason Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CRS-207 + Pembrolizumab

Arm Description

CRS-207 and pembrolizumab will be administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) will be administered by intravenous (IV) infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 colony-forming units [CFU]) will be administered by IV infusion over 1 hour on Day 2. If the infusions are well tolerated, pembrolizumab and CRS-207 may be administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab will continue to be administered on Day 1 at each treatment cycle (every 3 weeks); CRS-207 will be administered once every 6 weeks (every other cycle). Treatment will continue for up to 35 cycles as long as there is adequate safety and potential for clinical benefit.

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR)
ORR was evaluated based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each evaluable subject as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR RECIST v1.1 values of CR, PR, SD, PD, and NE are provided for this outcome measure. .

Secondary Outcome Measures

Disease Control Rate (DCR)
The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per RECIST v1.1.
Progression-Free Survival (PFS)
Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) according to RECIST v1.1 or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). Subjects who do not experience PD and are alive on or before the data cut-off date will be censored at the time of last evaluable tumor assessment or data cut-off date, whichever is earlier.
Duration of Response (DOR)
Number of weeks from the first date a study subject achieved an objective disease response of CR or PR according to RECIST v1.1 to the date a study subject exhibited PD or death due to any cause, estimated using KM methods with 95% CIs. Subjects who do not experience PD or death at the time of analysis will be censored at the time of last evaluable tumor assessment or data cut-off date, whichever is earlier.
Overall Survival (OS)
Number of weeks from the date of first dose of study treatment to the date of death from any cause, estimated using KM methods with 95% CIs for subjects in the SAF. Subjects without documentation of death at the time of analysis were censored as of the date the subject was last known to be alive, or the data cut-off date, whichever is earlier.

Full Information

First Posted
April 4, 2017
Last Updated
March 22, 2019
Sponsor
Aduro Biotech, Inc.
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03122548
Brief Title
Safety and Efficacy of CRS-207 With Pembrolizumab in Gastric, Gastroesophageal Junction or Esophageal Cancers
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Terminated
Why Stopped
Low enrollment and lack of clinical activity in other CRS-207 studies.
Study Start Date
August 14, 2017 (Actual)
Primary Completion Date
December 27, 2017 (Actual)
Study Completion Date
January 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aduro Biotech, Inc.
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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 chemotherapy regimens for advanced disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma
Keywords
stomach cancer, gastric cancer, esophageal cancer, digestive system diseases, gastrointestinal diseases, stomach diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CRS-207 + Pembrolizumab
Arm Type
Experimental
Arm Description
CRS-207 and pembrolizumab will be administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) will be administered by intravenous (IV) infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 colony-forming units [CFU]) will be administered by IV infusion over 1 hour on Day 2. If the infusions are well tolerated, pembrolizumab and CRS-207 may be administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab will continue to be administered on Day 1 at each treatment cycle (every 3 weeks); CRS-207 will be administered once every 6 weeks (every other cycle). Treatment will continue for up to 35 cycles as long as there is adequate safety and potential for clinical benefit.
Intervention Type
Biological
Intervention Name(s)
CRS-207
Intervention Description
Administered by IV infusion over 1 hour.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK-3475
Intervention Description
Administered by IV infusion over 30 minutes.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
ORR was evaluated based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each evaluable subject as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR RECIST v1.1 values of CR, PR, SD, PD, and NE are provided for this outcome measure. .
Time Frame
BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
Secondary Outcome Measure Information:
Title
Disease Control Rate (DCR)
Description
The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per RECIST v1.1.
Time Frame
BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
Title
Progression-Free Survival (PFS)
Description
Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) according to RECIST v1.1 or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). Subjects who do not experience PD and are alive on or before the data cut-off date will be censored at the time of last evaluable tumor assessment or data cut-off date, whichever is earlier.
Time Frame
Subjects followed for disease progression from first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
Title
Duration of Response (DOR)
Description
Number of weeks from the first date a study subject achieved an objective disease response of CR or PR according to RECIST v1.1 to the date a study subject exhibited PD or death due to any cause, estimated using KM methods with 95% CIs. Subjects who do not experience PD or death at the time of analysis will be censored at the time of last evaluable tumor assessment or data cut-off date, whichever is earlier.
Time Frame
DOR assessed from the date of a post-baseline tumor assessment of CR or PR per RECIST v1.1 until the date of documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
Title
Overall Survival (OS)
Description
Number of weeks from the date of first dose of study treatment to the date of death from any cause, estimated using KM methods with 95% CIs for subjects in the SAF. Subjects without documentation of death at the time of analysis were censored as of the date the subject was last known to be alive, or the data cut-off date, whichever is earlier.
Time Frame
OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 15 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) Confirmed recurrent or metastatic disease Received and experienced disease progression on, or following one or two prior chemotherapy regimens for advanced disease. 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. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Can provide tissue for PD-L1 and mesothelin biomarker analysis Adequate organ and marrow function at screening Exclusion Criteria: Diagnosis of squamous or undifferentiated gastric cancer Individuals with inaccessible tumors or for whom biopsy is contraindicated 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 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 Clinical evidence of ascites by physical exam 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 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 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.
Facility Information:
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Mary Crowley Cancer Research
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Virginia Mason Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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