Trial Outcomes & Findings for Evaluation of CRS-207 With Pembrolizumab in Previously Treated Malignant Pleural Mesothelioma (MPM) (NCT NCT03175172)

NCT ID: NCT03175172

Last Updated: 2019-04-04

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 10 participants
• Primary outcome timeframe: 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.
• Results posted on: 2019-04-04

Participant Flow

Participant milestones

Measure	Experimental 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).
Overall Study STARTED	10
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Measure	Experimental 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).
Overall Study Death	3
Overall Study Withdrawal by Subject	3
Overall Study Lost to Follow-up	1
Overall Study Study Terminated by Sponsor	3

Baseline Characteristics

Evaluation of CRS-207 With Pembrolizumab in Previously Treated Malignant Pleural Mesothelioma (MPM)

Baseline characteristics by cohort

Measure	Experimental n=10 Participants 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).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants
Age, Continuous	64.7 years STANDARD_DEVIATION 13.08 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Measure	Experimental n=9 Participants 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 Response Rate (ORR) Complete Response	0 Participants
Overall Response Rate (ORR) Partial Response	0 Participants
Overall Response Rate (ORR) Stable Disease	1 Participants
Overall Response Rate (ORR) Progressive Disease	8 Participants
Overall Response Rate (ORR) Not Evaluable	0 Participants

SECONDARY outcome

Timeframe: 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.

Population: 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.

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

Outcome measures

Measure	Experimental n=9 Participants 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).
Disease Control Rate (DCR) Complete Response	0 Participants
Disease Control Rate (DCR) Partial Response	0 Participants
Disease Control Rate (DCR) Stable Disease	3 Participants
Disease Control Rate (DCR) Progressive Disease	6 Participants
Disease Control Rate (DCR) Not Evaluable	0 Participants

SECONDARY outcome

Timeframe: 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.

Population: Analysis of PFS was performed on subjects in the SAF.

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.

Outcome measures

Measure

Experimental n=10 Participants 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).

Progression-Free Survival (PFS)

6 weeks Interval 3.43 to 7.14

SECONDARY outcome

Timeframe: 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.

Population: Analysis of FVC was performed on all subjects in the SAF. No subjects showed improvement in FVC.

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

Outcome measures

Measure

Experimental n=10 Participants 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).

Improvement in Pulmonary Function

0 Participants

SECONDARY outcome

Timeframe: OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 25 weeks.

Population: Analysis of OS was performed on subjects in the SAF.

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.

Outcome measures

Measure

Experimental n=10 Participants 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 Survival (OS)

12.57 weeks Interval 8.14 to 18.14

Adverse Events

Experimental

Serious events: 4 serious events

Other events: 10 other events

Deaths: 3 deaths

Serious adverse events

Measure	Experimental n=10 participants at risk 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).
Respiratory, thoracic and mediastinal disorders DYSPNOEA	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders HYPOXIA	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Vascular disorders HYPOTENSION	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.

Other adverse events

Measure	Experimental n=10 participants at risk 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).
General disorders CHILLS	100.0% 10/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
General disorders PYREXIA	90.0% 9/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
General disorders OEDEMA PERIPHERAL	30.0% 3/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
General disorders FATIGUE	20.0% 2/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
General disorders OEDEMA	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	40.0% 4/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders HYPOXIA	30.0% 3/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders COUGH	20.0% 2/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders DYSPNOEA EXERTIONAL	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Respiratory, thoracic and mediastinal disorders WHEEZING	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders NAUSEA	40.0% 4/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders CONSTIPATION	20.0% 2/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders VOMITING	20.0% 2/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders ABDOMINAL PAIN	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders DRY MOUTH	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Vascular disorders HYPOTENSION	40.0% 4/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Vascular disorders HOT FLUSH	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Vascular disorders HYPERTENSION	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Vascular disorders THROMBOPHLEBITIS SUPERFICIAL	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders ANAEMIA	50.0% 5/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders DECREASED APPETITE	30.0% 3/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders HYPOALBUMINAEMIA	20.0% 2/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders HYPOMAGNESAEMIA	20.0% 2/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders HYPERGLYCAEMIA	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders HYPERNATRAEMIA	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Musculoskeletal and connective tissue disorders BACK PAIN	30.0% 3/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Musculoskeletal and connective tissue disorders MYALGIA	20.0% 2/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Musculoskeletal and connective tissue disorders NECK PAIN	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Investigations LYMPHOCYTE COUNT DECREASED	20.0% 2/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Investigations BLOOD CREATININE INCREASED	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Investigations WEIGHT DECREASED	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Cardiac disorders TACHYCARDIA	20.0% 2/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Cardiac disorders ATRIAL FIBRILLATION	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Cardiac disorders SINUS TACHYCARDIA	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Infections and infestations CANDIDA INFECTION	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Infections and infestations GINGIVITIS	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Infections and infestations PNEUMONIA	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Nervous system disorders DYSGEUSIA	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Nervous system disorders HEADACHE	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders NIGHT SWEATS	20.0% 2/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders PETECHIAE	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Injury, poisoning and procedural complications PROCEDURAL PAIN	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Psychiatric disorders RESTLESSNESS	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Renal and urinary disorders ACUTE KIDNEY INJURY	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Reproductive system and breast disorders BREAST OEDEMA	10.0% 1/10 • 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. AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.

Additional Information

Medical Affairs

Aduro Biotech, Inc.

Phone: 510.809.2452

Email: MedicalAffairs@aduro.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER