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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.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malignant Pleural Mesothelioma
Interventions Biological: CRS-207
Biological: Pembrolizumab
Enrollment 10
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Experimental
Hide Arm/Group Description CRS-207 and pembrolizumab were administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) was administered by intravenous (IV) infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 colony forming units [CFU]) was administered by IV infusion over 1 hour on Day 2. If tolerated, pembrolizumab and CRS-207 were administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab continued to be administered on Day 1 at each treatment cycle (every 3 weeks); and CRS-207 was administered once every 6 weeks (every other cycle).
Period Title: Overall Study
Started 10
Completed 0
Not Completed 10
Reason Not Completed
Death             3
Withdrawal by Subject             3
Lost to Follow-up             1
Study Terminated by Sponsor             3
Arm/Group Title Experimental
Hide Arm/Group Description CRS-207 and pembrolizumab were administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) was administered by IV infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 CFU) was administered by IV infusion over 1 hour on Day 2. If tolerated, pembrolizumab and CRS-207 were administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab continued to be administered on Day 1 at each treatment cycle (every 3 weeks); and CRS-207 was administered once every 6 weeks (every other cycle).
Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
Baseline analysis provided for all subjects who were administered at least 1 dose of protocol-specified drug (the Safety Analysis Set [SAF]).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
<=18 years
0
   0.0%
Between 18 and 65 years
4
  40.0%
>=65 years
6
  60.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants
64.7  (13.08)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
5
  50.0%
Male
5
  50.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Black or African American
1
  10.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
White
7
  70.0%
Other
1
  10.0%
Not Reported
1
  10.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Hispanic or Latino
2
  20.0%
Not Hispanic or Latino
8
  80.0%
Not Reported
0
   0.0%
1.Primary Outcome
Title Overall Response Rate (ORR)
Hide 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 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis based on subjects who received ≥1 dose of study treatment and had ≥1 evaluable post-baseline modified RECIST for MPM tumor response assessment or were discontinued due to toxicity (the Evaluable Analysis Set [EAS]). 1 subject did not have post-baseline tumor response assessments and could not be evaluated for this outcome measure.
Arm/Group Title Experimental
Hide Arm/Group Description:
CRS-207 and pembrolizumab were administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) was administered by IV infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 CFU) was administered by IV infusion over 1 hour on Day 2. If tolerated, pembrolizumab and CRS-207 were administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab continued to be administered on Day 1 at each treatment cycle (every 3 weeks); and CRS-207 was administered once every 6 weeks (every other cycle).
Overall Number of Participants Analyzed 9
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
Partial Response
0
   0.0%
Stable Disease
1
  11.1%
Progressive Disease
8
  88.9%
Not Evaluable
0
   0.0%
2.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per modified RECIST for MPM.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis based on subjects who received ≥1 dose of study treatment and had ≥1 evaluable post-baseline modified RECIST for MPM tumor response assessment or were discontinued due to toxicity (the Evaluable Analysis Set [EAS]). 1 subject did not have post-baseline tumor response assessments and could not be evaluated for this outcome measure.
Arm/Group Title Experimental
Hide Arm/Group Description:
CRS-207 and pembrolizumab were administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) was administered by IV infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 CFU) was administered by IV infusion over 1 hour on Day 2. If tolerated, pembrolizumab and CRS-207 were administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab continued to be administered on Day 1 at each treatment cycle (every 3 weeks); and CRS-207 was administered once every 6 weeks (every other cycle).
Overall Number of Participants Analyzed 9
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
Partial Response
0
   0.0%
Stable Disease
3
  33.3%
Progressive Disease
6
  66.7%
Not Evaluable
0
   0.0%
3.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of PFS was performed on subjects in the SAF.
Arm/Group Title Experimental
Hide Arm/Group Description:
CRS-207 and pembrolizumab were administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) was administered by IV infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 CFU) was administered by IV infusion over 1 hour on Day 2. If tolerated, pembrolizumab and CRS-207 were administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab continued to be administered on Day 1 at each treatment cycle (every 3 weeks); and CRS-207 was administered once every 6 weeks (every other cycle).
Overall Number of Participants Analyzed 10
Median (95% Confidence Interval)
Unit of Measure: weeks
6
(3.43 to 7.14)
4.Secondary Outcome
Title Improvement in Pulmonary Function
Hide Description 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
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of FVC was performed on all subjects in the SAF. No subjects showed improvement in FVC.
Arm/Group Title Experimental
Hide Arm/Group Description:
CRS-207 and pembrolizumab were administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) was administered by IV infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 CFU) was administered by IV infusion over 1 hour on Day 2. If tolerated, pembrolizumab and CRS-207 were administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab continued to be administered on Day 1 at each treatment cycle (every 3 weeks); and CRS-207 was administered once every 6 weeks (every other cycle).
Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
5.Secondary Outcome
Title Overall Survival (OS)
Hide 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 25 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of OS was performed on subjects in the SAF.
Arm/Group Title Experimental
Hide Arm/Group Description:
CRS-207 and pembrolizumab were administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) was administered by IV infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 CFU) was administered by IV infusion over 1 hour on Day 2. If tolerated, pembrolizumab and CRS-207 were administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab continued to be administered on Day 1 at each treatment cycle (every 3 weeks); and CRS-207 was administered once every 6 weeks (every other cycle).
Overall Number of Participants Analyzed 10
Median (95% Confidence Interval)
Unit of Measure: weeks
12.57
(8.14 to 18.14)
Time Frame Subjects were followed for serious and non-serious adverse events (AEs) from the beginning of any study drug until 28 days following the last dose of study drug or initiation of a subsequent cancer-related therapy, whichever is earlier, an average of 3 months. Subjects were followed for survival for 12 months after end-of-treatment (EOT) or until study termination on 31 January 2018, whichever is earlier, an average of 14 weeks.
Adverse Event Reporting Description AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
 
Arm/Group Title Experimental
Hide Arm/Group Description CRS-207 and pembrolizumab were administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) was administered by IV infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 CFU) was administered by IV infusion over 1 hour on Day 2. If tolerated, pembrolizumab and CRS-207 were administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab continued to be administered on Day 1 at each treatment cycle (every 3 weeks); and CRS-207 was administered once every 6 weeks (every other cycle).
All-Cause Mortality
Experimental
Affected / at Risk (%)
Total   3/10 (30.00%) 
Hide Serious Adverse Events
Experimental
Affected / at Risk (%)
Total   4/10 (40.00%) 
Respiratory, thoracic and mediastinal disorders   
DYSPNOEA * 1  1/10 (10.00%) 
HYPOXIA * 1  1/10 (10.00%) 
PNEUMONITIS  1  1/10 (10.00%) 
Vascular disorders   
HYPOTENSION  1  1/10 (10.00%) 
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Experimental
Affected / at Risk (%)
Total   10/10 (100.00%) 
Blood and lymphatic system disorders   
ANAEMIA * 1  5/10 (50.00%) 
Cardiac disorders   
TACHYCARDIA * 1  2/10 (20.00%) 
ATRIAL FIBRILLATION  1  1/10 (10.00%) 
SINUS TACHYCARDIA  1  1/10 (10.00%) 
Gastrointestinal disorders   
NAUSEA * 1  4/10 (40.00%) 
CONSTIPATION  1  2/10 (20.00%) 
VOMITING  1  2/10 (20.00%) 
ABDOMINAL PAIN  1  1/10 (10.00%) 
DRY MOUTH  1  1/10 (10.00%) 
General disorders   
CHILLS * 1  10/10 (100.00%) 
PYREXIA  1  9/10 (90.00%) 
OEDEMA PERIPHERAL  1  3/10 (30.00%) 
FATIGUE  1  2/10 (20.00%) 
OEDEMA  1  1/10 (10.00%) 
Infections and infestations   
CANDIDA INFECTION * 1  1/10 (10.00%) 
GINGIVITIS  1  1/10 (10.00%) 
PNEUMONIA  1  1/10 (10.00%) 
Injury, poisoning and procedural complications   
PROCEDURAL PAIN  1  1/10 (10.00%) 
Investigations   
LYMPHOCYTE COUNT DECREASED * 1  2/10 (20.00%) 
BLOOD CREATININE INCREASED  1  1/10 (10.00%) 
WEIGHT DECREASED  1  1/10 (10.00%) 
Metabolism and nutrition disorders   
DECREASED APPETITE * 1  3/10 (30.00%) 
HYPOALBUMINAEMIA  1  2/10 (20.00%) 
HYPOMAGNESAEMIA  1  2/10 (20.00%) 
HYPERGLYCAEMIA  1  1/10 (10.00%) 
HYPERNATRAEMIA  1  1/10 (10.00%) 
Musculoskeletal and connective tissue disorders   
BACK PAIN * 1  3/10 (30.00%) 
MYALGIA  1  2/10 (20.00%) 
MUSCULOSKELETAL CHEST PAIN  1  1/10 (10.00%) 
MUSCULOSKELETAL PAIN  1  1/10 (10.00%) 
NECK PAIN  1  1/10 (10.00%) 
Nervous system disorders   
DYSGEUSIA * 1  1/10 (10.00%) 
HEADACHE  1  1/10 (10.00%) 
Psychiatric disorders   
RESTLESSNESS  1  1/10 (10.00%) 
Renal and urinary disorders   
ACUTE KIDNEY INJURY  1  1/10 (10.00%) 
Reproductive system and breast disorders   
BREAST OEDEMA  1  1/10 (10.00%) 
Respiratory, thoracic and mediastinal disorders   
DYSPNOEA * 1  4/10 (40.00%) 
HYPOXIA  1  3/10 (30.00%) 
COUGH  1  2/10 (20.00%) 
DYSPNOEA EXERTIONAL  1  1/10 (10.00%) 
PNEUMONITIS  1  1/10 (10.00%) 
WHEEZING  1  1/10 (10.00%) 
Skin and subcutaneous tissue disorders   
NIGHT SWEATS  1  2/10 (20.00%) 
PETECHIAE  1  1/10 (10.00%) 
Vascular disorders   
HYPOTENSION * 1  4/10 (40.00%) 
HOT FLUSH  1  1/10 (10.00%) 
HYPERTENSION  1  1/10 (10.00%) 
THROMBOPHLEBITIS SUPERFICIAL  1  1/10 (10.00%) 
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
Study was terminated early and included a small number of subjects, and insufficient data were available to evaluate the clinical activity of the study treatment. Due to low enrollment, some protocol-specified outcome measures were not evaluated.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction is that study results will first be published in a joint multi-center paper unless (a) written confirmation is provided to the site or PI indicating that there will be no multi-center publication, or (b) at least 15 months have passed after the completion of data analysis at all study sites. Publications will be submitted for sponsor review ≥ 30 days prior to the publication date. Sponsor cannot require changes to the communication or extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Affairs
Organization: Aduro Biotech, Inc.
Phone: 510.809.2452
EMail: MedicalAffairs@aduro.com
Layout table for additonal information
Responsible Party: Aduro Biotech, Inc.
ClinicalTrials.gov Identifier: NCT03175172    
Other Study ID Numbers: ADU-CL-13
KEYNOTE KN-701 ( Other Identifier: (Other Identifier: Merck Sharp & Dohme Corp) )
First Submitted: June 1, 2017
First Posted: June 5, 2017
Results First Submitted: January 26, 2019
Results First Posted: February 19, 2019
Last Update Posted: April 4, 2019