- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03175172
Evaluation of CRS-207 With Pembrolizumab in Previously Treated Malignant Pleural Mesothelioma (MPM)
March 22, 2019 updated by: Aduro Biotech, Inc.
A Phase 2 Single-arm Study to Evaluate Safety and Efficacy of CRS-207 With Pembrolizumab in Adults With Previously-Treated Malignant Pleural Mesothelioma
The purpose of this study is to evaluate whether CRS-207 with pembrolizumab is safe and effective in adults with MPM who have failed prior anti-cancer therapy.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
The population for this study will consist of approximately 35 adults with histologically-confirmed MPM (epithelial or biphasic) whose disease has progressed after 1-2 prior anti-cancer therapies.
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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San Francisco, California, United States, 94115
- UCSF Comprehensive Cancer Center
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Florida
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center
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Illinois
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Chicago, Illinois, United States, 60637
- University of Chicago Medical Center
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Maryland
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Bethesda, Maryland, United States, 20892
- NIH National Cancer Institute
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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New York
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New York, New York, United States, 10016
- Laura & Isaac Perlmutter Cancer Center at NYU Langone
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic Foundation
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Abramson Cancer Center of the University of Pennsylvania
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologically-confirmed epithelial or biphasic MPM; biphasic tumors must have a predominantly (≥50%) epithelial component
- No more than 2 prior lines of anti-cancer therapy, one of which must have included pemetrexed and a platinum.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Adequate organ and marrow function
- Adequate lung function; forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) ≥ 45% of predicted value as measured by spirometry; and oxygen saturation ≥ 90% on room air
Exclusion Criteria
- Pleurodesis within 14 days prior to 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
- Active secondary malignancy
- Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug, or 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
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or agents targeting other checkpoint pathways (e.g. CTLA-4)
- Prior immunotherapy with CRS-207 or any other Listeria-based agent, therapeutic cancer vaccine, or adoptive T cell immunotherapy
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Experimental
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.
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Administered by IV infusion over approximately 1 hour.
Administered by IV infusion over approximately 30 minutes.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR)
Time Frame: BOR was assessed from the 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.
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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 assessed subject as measured by modified response evaluation criteria in solid tumors (modified RECIST) for MPM (Byrne and Nowak, 2004) 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.
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BOR was assessed from the 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.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Control Rate (DCR)
Time Frame: BOR was assessed from the 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.
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The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per modified RECIST for MPM.
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BOR was assessed from the 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.
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Progression-Free Survival (PFS)
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 9 weeks.
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Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) (per modified RECIST for MPM) or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CI).
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 tumor assessment or data cut-off date, whichever is earlier.
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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 9 weeks.
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Improvement in Pulmonary Function
Time Frame: Subjects tested by spirometry at Screening and up to 7 days prior to dosing every other cycle starting at Cycle 3 until 4 weeks post final dose, assessed up to 16 weeks.
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Percentage of subjects with improvement in forced vital capacity (FVC), defined as an increase from baseline of either ≥400 mL or ≥20% assessed using spirometry
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Subjects tested by spirometry at Screening and up to 7 days prior to dosing every other cycle starting at Cycle 3 until 4 weeks post final dose, assessed up to 16 weeks.
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Overall Survival (OS)
Time Frame: OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 25 weeks.
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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.
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OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 25 weeks.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 31, 2017
Primary Completion (Actual)
January 9, 2018
Study Completion (Actual)
January 31, 2018
Study Registration Dates
First Submitted
June 1, 2017
First Submitted That Met QC Criteria
June 2, 2017
First Posted (Actual)
June 5, 2017
Study Record Updates
Last Update Posted (Actual)
April 4, 2019
Last Update Submitted That Met QC Criteria
March 22, 2019
Last Verified
March 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Lung Neoplasms
- Adenoma
- Neoplasms, Mesothelial
- Pleural Neoplasms
- Mesothelioma
- Mesothelioma, Malignant
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Pembrolizumab
Other Study ID Numbers
- ADU-CL-13
- KEYNOTE KN-701 (Other Identifier: (Other Identifier: Merck Sharp & Dohme Corp))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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