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Trial record 1 of 3 for:    CRS-207 | mesothelioma
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Evaluation of CRS-207 With Pembrolizumab in Previously Treated Malignant Pleural Mesothelioma (MPM)

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ClinicalTrials.gov Identifier: NCT03175172
Recruitment Status : Terminated (Study was stopped due to low enrollment and lack of clinical activity.)
First Posted : June 5, 2017
Results First Posted : February 19, 2019
Last Update Posted : April 4, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Aduro Biotech, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Malignant Pleural Mesothelioma Biological: CRS-207 Biological: Pembrolizumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Single-arm Study to Evaluate Safety and Efficacy of CRS-207 With Pembrolizumab in Adults With Previously-Treated Malignant Pleural Mesothelioma
Actual Study Start Date : May 31, 2017
Actual Primary Completion Date : January 9, 2018
Actual Study Completion Date : January 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
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.
Biological: CRS-207
Administered by IV infusion over approximately 1 hour.

Biological: Pembrolizumab
Administered by IV infusion over approximately 30 minutes.
Other Name: MK-3475




Primary Outcome Measures :
  1. 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. ]
    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.


Secondary Outcome Measures :
  1. 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. ]
    The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per modified RECIST for MPM.

  2. 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. ]
    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.

  3. 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. ]
    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

  4. 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. ]
    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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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically-confirmed epithelial or biphasic MPM; biphasic tumors must have a predominantly (≥50%) epithelial component
  2. No more than 2 prior lines of anti-cancer therapy, one of which must have included pemetrexed and a platinum.
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  4. Adequate organ and marrow function
  5. 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

  1. Pleurodesis within 14 days prior to first dose of study drug
  2. 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
  3. Active secondary malignancy
  4. 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
  5. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study drug
  6. History of (non-infectious) pneumonitis that required steroids or current pneumonitis
  7. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or agents targeting other checkpoint pathways (e.g. CTLA-4)
  8. Prior immunotherapy with CRS-207 or any other Listeria-based agent, therapeutic cancer vaccine, or adoptive T cell immunotherapy
  9. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03175172


Locations
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United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Maryland
NIH National Cancer Institute
Bethesda, Maryland, United States, 20892
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Laura & Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States, 10016
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Aduro Biotech, Inc.
Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Aduro Biotech, Inc.:
Study Protocol  [PDF] June 14, 2017
Statistical Analysis Plan  [PDF] March 22, 2018


Publications:
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Responsible Party: Aduro Biotech, Inc.
ClinicalTrials.gov Identifier: NCT03175172     History of Changes
Other Study ID Numbers: ADU-CL-13
KEYNOTE KN-701 ( Other Identifier: (Other Identifier: Merck Sharp & Dohme Corp) )
First Posted: June 5, 2017    Key Record Dates
Results First Posted: February 19, 2019
Last Update Posted: April 4, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents