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(NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT02508532
Recruitment Status : Completed
First Posted : July 27, 2015
Results First Posted : June 22, 2021
Last Update Posted : July 2, 2021
Sponsor:
Information provided by (Responsible Party):
Blueprint Medicines Corporation

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Gastrointestinal Stromal Tumors (GIST)
Other Relapsed or Refractory Solid Tumors
Intervention Drug: Avapritinib
Enrollment 250
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 300 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 400 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 or 400 mg QD
Hide Arm/Group Description

Part 1: Patients received a starting dose of 30 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 60 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 90 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 135 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 200 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation. .

Part 1: Patients received a starting dose of 300 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 400 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 600 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1 and Part 2: Patients enrolled in Part 1 and Part 2 at a starting dose of 300 or 400 mg QD were included in the Part1/Part 2 safety and efficacy analysis.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Period Title: Part 1 - Dose Determining Period
Started 6 6 6 6 6 6 7 3 0 [1]
Patients From Part 1 Included in the Part 2 Analyses 0 0 0 0 0 6 7 0 0
Completed 6 6 6 6 6 6 6 2 0
Not Completed 0 0 0 0 0 0 1 1 0
Reason Not Completed
did not complete >21 days of treatment             0             0             0             0             0             0             1             0             0
Not Evaluable             0             0             0             0             0             0             0             1             0
[1]
This group includes patients enrolled in Part 1 and Part 2 at a starting dose of 300 or 400 mg QD. This group was not used to determine the MTD in Part 1
Period Title: Part 2 - Treatment
Started 0 [1] 0 [1] 0 [1] 0 [1] 0 [1] 0 [2] 0 [3] 0 [1] 217 [4]
Completed 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 217
Reason Not Completed
Disease Progression             0             0             0             0             0             0             0             0             118
Adverse Event             0             0             0             0             0             0             0             0             49
Physician Decision             0             0             0             0             0             0             0             0             12
Administrative             0             0             0             0             0             0             0             0             3
Sponsor Decision             0             0             0             0             0             0             0             0             28
Death             0             0             0             0             0             0             0             0             1
Withdrawal by Subject             0             0             0             0             0             0             0             0             6
[1]
These patients are not included in Part 2 analyses
[2]

Part 1 Only:

6 Patients from this group are included in the 300 or 400 mg QD group.

[3]

Part 1 Only:

7 Patients from this group are included in the 300 or 400 mg QD group.

[4]
Includes 13 patients enrolled in Part 1 at a starting dose of 300 mg (n = 6) or 400 mg (n = 7) QD.
Period Title: Part 1 and Part 2 End of Study
Started 6 6 6 6 6 0 [1] 0 [2] 3 217 [3]
Completed 0 0 0 0 0 0 0 0 0
Not Completed 6 6 6 6 6 0 0 3 217
Reason Not Completed
Disease Progression             2             0             0             0             0             0             0             1             6
Adverse Event             1             0             1             0             0             0             0             0             2
Death             0             4             2             4             3             0             0             1             111
Lost to Follow-up             1             1             1             0             0             0             0             0             6
Withdrawal by Subject             0             0             0             0             0             0             0             0             15
Physician Decision             0             0             1             0             1             0             0             0             8
Initiation of another therapy             0             0             0             0             0             0             0             0             1
Sponsor Decision             2             1             1             2             2             0             0             1             67
Continuing in study             0             0             0             0             0             0             0             0             1
[1]
These 6 patients are included in the 300 or 400 mg QD dose group
[2]
These 7 patients are included in the 300 or 400 mg QD dose group
[3]
Includes 13 patients enrolled in Part 1 at a starting dose of 300 mg (n = 6) or 400 mg (n = 7) QD.
Arm/Group Title Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 mg or 400 mg QD Total
Hide Arm/Group Description

Part 1: Patients received a starting dose of 30 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 60 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 90 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 135 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 200 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation. .

Part 1: Patients received a starting dose of 600 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1 and Part 2: Patients enrolled in Part 1 and Part 2 at a starting dose of 300 or 400 mg QD were included in the Part1/Part 2 safety and efficacy analysis.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Includes 13 patients from Part 1

Total of all reporting groups
Overall Number of Baseline Participants 6 6 6 6 6 3 217 250
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
58.7  (12.21) 60.2  (6.77) 60.2  (11.84) 61.5  (10.05) 61.7  (8.31) 48.3  (20.82) 59.4  (11.00) 59.4  (10.97)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
Female
4
  66.7%
3
  50.0%
1
  16.7%
0
   0.0%
3
  50.0%
1
  33.3%
84
  38.7%
96
  38.4%
Male
2
  33.3%
3
  50.0%
5
  83.3%
6
 100.0%
3
  50.0%
2
  66.7%
133
  61.3%
154
  61.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.9%
2
   0.8%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
22
  10.1%
22
   8.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.5%
1
   0.4%
Black or African American
1
  16.7%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
10
   4.6%
12
   4.8%
White
5
  83.3%
6
 100.0%
4
  66.7%
5
  83.3%
4
  66.7%
3
 100.0%
154
  71.0%
181
  72.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
2
  33.3%
0
   0.0%
2
  33.3%
0
   0.0%
28
  12.9%
32
  12.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Belgium Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
0 0 1 1 1 0 13 16
France Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
0 0 1 1 2 0 20 24
Germany Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
1 2 0 1 0 0 14 18
Netherlands Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
0 0 1 0 0 0 11 12
Poland Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
0 0 0 0 0 0 8 8
South Korea Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
0 0 0 0 0 0 17 17
Spain Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
0 0 0 0 0 0 11 11
United Kingdom Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
1 0 3 0 0 1 23 28
United States Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 3 participants 217 participants 250 participants
4 4 0 3 3 2 100 116
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 3 participants 6 participants 6 participants 6 participants 6 participants 3 participants 198 participants 228 participants
24.78  (4.22) 31.61  (8.63) 28.33  (3.76) 23.78  (2.71) 24.63  (5.16) 27.15  (4.54) 25.98  (6.22) 26.09  (6.15)
[1]
Measure Analysis Population Description: Body Mass Index was only calculated for patients with both a height and weight measurement at Baseline
1.Primary Outcome
Title Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib
Hide Description Patients with event(s) of dose-limiting toxicity
Time Frame Cycle 1 (28 days) of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Patients that completed Part 1 or had a DLT
Arm/Group Title Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 300 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 400 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD
Hide Arm/Group Description:

Part 1: Patients received a starting dose of 30 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 60 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 90 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 135 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 200 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation. .

Part 1: Patients received a starting dose of 300 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation. Patients that received at least one dose of avapritinib were included in the Part 2 analysis.

Part 1: Patients received a starting dose of 400 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Patients that received at least one dose of avapritinib were included in the Part 2 analysis.

Part 1: Patients received a starting dose of 600 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Overall Number of Participants Analyzed 6 6 6 6 6 6 6 2
Measure Type: Number
Unit of Measure: patients with event(s) of dose-limiting
0 0 0 0 0 0 0 2
2.Primary Outcome
Title Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE)
Hide Description The overall safety profile of the drug was assessed by reviewing the number of patients with AEs, SAEs and other events. There was no formal statistical analysis. Safety assessments continued for the duration of treatment.
Time Frame AEs were collected from the start of study drug until 30 days after the last dose, SAEs were collected from the date of the informed consent signature until 30 days after the last dose of study drug, up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population - all patients that received at least one dose of avapritinib
Arm/Group Title Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 mg or 400 mg QD
Hide Arm/Group Description:

Part 1: Patients received a starting dose of 30 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 60 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 90 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 135 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 200 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation. .

Part 1: Patients received a starting dose of 600 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1 and Part 2: Patients enrolled in Part 1 and Part 2 at a starting dose of 300 or 400 mg QD were included in the Part1/Part 2 safety and efficacy analysis. 13 patients in this group were enrolled in Part 1

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Overall Number of Participants Analyzed 6 6 6 6 6 3 217
Measure Type: Number
Unit of Measure: participants
Participants with an Adverse Event 6 6 6 6 6 3 216
Participants with a Serious Adverse Event 3 4 5 5 5 3 140
3.Primary Outcome
Title Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1
Hide Description To evaluate objective response rate (ORR) determined by central radiology assessment per mRECIST, version 1.1 in patients with advanced GIST treated with avapritinib. A complete response per modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) is defined as complete disappearance of all target lesions. A partial response is defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Overall Response (OR) = CR + PR
Time Frame Tumor assessments were performed at screening, Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter up to approximately 4 years. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg, including 13 patients enrolled in Part 1
Arm/Group Title Patients With a PDGFRA D842V Mutation 2L Patients Without a PDGFRA D842V Mutation 3L Patients Without a PDGFRA D842V Mutation
Hide Arm/Group Description:
Patients with a PDGFRA D842V Mutation, any line of treatment
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Overall Number of Participants Analyzed 38 50 128
Measure Type: Count of Participants
Unit of Measure: Participants
Responder
36
  94.7%
10
  20.0%
20
  15.6%
Non-Responder
2
   5.3%
40
  80.0%
108
  84.4%
4.Secondary Outcome
Title Maximum Plasma Drug Concentration (Cmax)
Hide Description Maximum plasma drug concentration (Cmax) following a single dose of avapritinib
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Arm/Group Title Part 1 Avapritinib (Formerly BLU-285) 300 mg QD Part 1 Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 113 50
Median (Standard Deviation)
Unit of Measure: ng/mL
305  (153) 343  (181)
5.Secondary Outcome
Title Time to Maximum Plasma Drug Concentration (Tmax)
Hide Description Cycle 1 Day 1 PK time to maximum plasma drug concentration (Tmax)
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 and Part 2 with available samples for PK
Arm/Group Title Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 113 50
Median (Full Range)
Unit of Measure: hours
4.0
(0.98 to 23.5)
4.02
(1.97 to 24.0)
6.Secondary Outcome
Title Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose (C24)
Hide Description Plasma drug concentration at 24 hours postdose prior to the next daily dose (C24) following a single dose of avapritinib
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
Arm/Group Title Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 36 19
Mean (Standard Deviation)
Unit of Measure: ng/mL
134  (49.4) 185  (80.2)
7.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC 0-24)
Hide Description Area under the plasma concentration-time curve from time 0 to 24 hours (AUC 0-24) following a single dose of avapritinib
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
Arm/Group Title Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 36 19
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
4510  (1760) 5310  (2080)
8.Secondary Outcome
Title Apparent Oral Clearance Unadjusted for Bioavailability (CL/F)
Hide Description Apparent oral clearance unadjusted for bioavailability (CL/F) following a single dose of avapritinib
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
Arm/Group Title Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 23 8
Mean (Standard Deviation)
Unit of Measure: L/h
31.5  (15.2) 29.9  (20.1)
9.Secondary Outcome
Title Apparent Volume of Distribution, Unadjusted for Bioavailability (Vz/F)
Hide Description Apparent volume of distribution, unadjusted for bioavailability (Vz/F) following a single dose of avapritinib
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
Arm/Group Title Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 23 8
Mean (Standard Error)
Unit of Measure: L
1310  (676) 1340  (597)
10.Secondary Outcome
Title Terminal Elimination Half-life (t1/2)
Hide Description Terminal elimination half-life (t1/2) following a single dose of avapritinib
Time Frame Cycle 1 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
Arm/Group Title Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 23 8
Mean (Standard Deviation)
Unit of Measure: h
32.1  (15.6) 43.5  (28.4)
11.Secondary Outcome
Title Maximum Plasma Drug Concentration (Cmax) at Steady State
Hide Description Maximum plasma drug concentration (Cmax) at steady state following 15 days of QD dosing
Time Frame Cycle 1 Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Arm/Group Title Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 110 38
Mean (Standard Deviation)
Unit of Measure: ng/mL
905  (402) 1140  (469)
12.Secondary Outcome
Title Time of Maximal Concentration (Tmax) at Steady State
Hide Description Time of maximal concentration (Tmax) at steady state following 15 days of QD dosing
Time Frame Cycle 1 Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Arm/Group Title Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 110 38
Median (Full Range)
Unit of Measure: h
4.0
(0.0 to 8.17)
3.99
(0.5 to 8.0)
13.Secondary Outcome
Title Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at Steady State (C24,ss)
Hide Description Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at steady state (C24,ss) following 15 days of QD dosing
Time Frame Cycle 1 Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Arm/Group Title Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 110 38
Mean (Standard Deviation)
Unit of Measure: ng/mL
593  (263) 760  (343)
14.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady Sate (AUC0-τ,ss) (τ=24 h)
Hide Description Area under the plasma concentration-time curve over the dosing interval at steady sate (AUC0-τ,ss) (τ=24 h) following 15 days of QD dosing
Time Frame Cycle 1 Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Arm/Group Title Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 110 38
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
16900  (7230) 21300  (9250)
15.Secondary Outcome
Title Progression-free Survival Per mRECIST Version 1.1
Hide Description Progression-free survival is defined as the time in months from the start of treatment to the date of first documented progression or death due to any cause. Progression-free survival determined by central radiological assessment per modified Response Evaluation Criteria in Solid Tumors (mRECIST), version 1.1 in patients with advanced GIST. A progressively growing tumor must meet the following criteria: a) the target lesions must be greater or equal to 2cm in size and be a new GIST active lesion or b) the target lesions must be expanding on at least 2 sequential imaging studies.
Time Frame Tumor assessments were performed at screening, Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter up to approximately 4 years. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD
Arm/Group Title Patients With a PDGFRA D842V Mutation 2L Patients Without a PDGFRA D842V Mutation 3L Patients Without a PDGFRA D842V Mutation
Hide Arm/Group Description:
Patients with a PDGFRA D842V mutation, any line of treatment
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Overall Number of Participants Analyzed 38 50 128
Median (95% Confidence Interval)
Unit of Measure: months
27.6 [1] 
(19.5 to NA)
5.5
(2.0 to 9.4)
3.7
(3.6 to 5.6)
[1]
The upper bounds of the confidence interval could not be calculated
16.Secondary Outcome
Title Apparent Oral Clearance at Steady State, Unadjusted for Bioavailability (CLss/F)
Hide Description Apparent oral clearance at steady state, unadjusted for bioavailability (CLss/F) following 15 days of QD dosing
Time Frame Cycle 1 Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Arm/Group Title Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Hide Arm/Group Description:
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Overall Number of Participants Analyzed 110 38
Mean (Standard Deviation)
Unit of Measure: L/h
21.8  (12.0) 22.8  (11.7)
17.Secondary Outcome
Title Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1
Hide Description Percent of patients with a complete response, partial response or stable disease lasting more than 16 weeks. A complete response per modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) is defined as complete disappearance of all target lesions. A partial response is defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Stable disease is defined as a tumor that does not meet the criteria for progression or for response. A progressively growing tumor must meet the following criteria: a) the target lesions must be greater or equal to 2cm in size and be a new GIST active lesion or b) the target lesions must be expanding on at least 2 sequential imaging studies.
Time Frame Tumor assessments were performed at screening, Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter up to approximately 4 years. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
patients with a starting dose of 300 or 400 mg QD
Arm/Group Title Patients With a PDGFRA D842V Mutation 2L Patients Without a PDGFRA D842V Mutation 3L Patients Without a PDGFRA D842V Mutation
Hide Arm/Group Description:
Patients with a PDGFRA D842V mutation, any line of treatment
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Overall Number of Participants Analyzed 38 50 128
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical Benefit
37
  97.4%
26
  52.0%
51
  39.8%
No Clinical Benefit
1
   2.6%
24
  48.0%
77
  60.2%
18.Secondary Outcome
Title Response Rate Determined by Central Radiology Assessment Per Choi Criteria
Hide Description A complete response is defined as complete disappearance of all target lesions. A partial response is ≥10% decrease tumor size at computed tomography (CT) or ≥15% decrease in tumor attenuation at computed tomography (CT) and no new lesions. The response rate is defined as complete response plus partial response.
Time Frame Tumor assessments were performed at screening, Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter up to approximately 4 years. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg
Arm/Group Title Patients With a PDGFRA D842V Mutation 2L Patients Without a PDGFRA D842V Mutation 3L Patients Without a PDGFRA D842V Mutation
Hide Arm/Group Description:
Patients with a PDGFRA D842V mutation, any line of treatment
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Overall Number of Participants Analyzed 38 50 128
Measure Type: Count of Participants
Unit of Measure: Participants
Responder
37
  97.4%
18
  36.0%
45
  35.2%
Non-responder
1
   2.6%
32
  64.0%
83
  64.8%
19.Secondary Outcome
Title Duration of Response Determined by Central Radiology Assessment Per mRECIST, Version 1.1
Hide Description

Duration from time to first documented CR/PR to date of first documented disease progression or death.

A complete response per modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) is defined as complete disappearance of all target lesions. A partial response is defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Overall Response (OR) = CR + PR

Time Frame Tumor assessments were performed at screening, Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter up to approximately 4 years. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD. Only patients that achieved a CR or PR are included in this analysis
Arm/Group Title Patients With PDGFRA D842V Mutation 2L Patients Without a PDGFRA D842V Mutation 3L Patients Without a PDGFRA D842V Mutation
Hide Arm/Group Description:
Patients with a PDGFRA D842V mutation, any line of treatment
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Overall Number of Participants Analyzed 36 10 20
Median (95% Confidence Interval)
Unit of Measure: months
22.1 [1] 
(14.3 to NA)
19.2
(9.2 to 19.2)
10.2
(7.2 to 15.0)
[1]
The upper bounds of the confidence interval could not be calculated
20.Secondary Outcome
Title Median PFS on Last Prior Anti-cancer Therapy
Hide Description Progression Free Survival (PFS) is defined as the time in months from the start of treatment to the date of first documented disease progression or death due to any cause, which ever occurs first. PFS on last prior anti-cancer therapy is defined as the time in months from the start of last prior anti-cancer therapy to progression on that therapy.
Time Frame Historical data collected at enrollment, all available data on prior therapy was collected
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled on any dose (Part 1 and Part 2) with data on progression-free survival for the most recent prior therapy
Arm/Group Title Patients With a PDGFRA D842V Mutation 2L Patients Without a PDGFRA D842V Mutation 3L Patients Without a PDGFRA D842V Mutation
Hide Arm/Group Description:
Patients with a PDGFRA D842V mutation, any line of treatment
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Overall Number of Participants Analyzed 45 51 142
Median (95% Confidence Interval)
Unit of Measure: months
5.9
(4.2 to 8.3)
31.0
(26.4 to 48.0)
6.4
(4.3 to 8.3)
21.Secondary Outcome
Title Change From Baseline in Levels of KIT and PDGFRα Mutant Allele Fractions in Peripheral Blood
Hide Description Change of mutant allele fraction (MAF) summarizes the largest fold change. Change from baseline only displayed for patients with pre and post treatment MAF measurements. A positive number represents an increase in MAF. Data is only provided for patients that had both a baseline measurement and an end of treatment measurement.
Time Frame Baseline and End of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD
Arm/Group Title Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 mg or 400 mg QD
Hide Arm/Group Description:

Part 1 and Part 2: Patients enrolled in Part 1 and Part 2 at a starting dose of 300 or 400 mg QD were included in the Part1/Part 2 safety and efficacy analysis.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Overall Number of Participants Analyzed 1
Mean (Standard Deviation)
Unit of Measure: fraction of total
Change in PDGFRA MAF 8.702 [1]   (NA)
Change in KIT MAF 14.398 [1]   (NA)
[1]
Only one patient had data for this outcome measure so the standard deviation cannot be calculated
22.Secondary Outcome
Title KIT, PDGFRA, and Other Cancer-relevant Mutations Present in Tumor Tissue at Baseline and EOT
Hide Description Change in mutations in tumor tissue at baseline and end of treatment (EOT). EOT tumor biopsies were optional and there were no EOT samples collected.
Time Frame Baseline and end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with pre-and post-treatment tumor biopsies. No patients provided a post-treatment biopsy.
Arm/Group Title Patients With a PDGFRA D842V Mutation 2L Patients Without a PDGFRA D842V Mutation 3L Patients Without a PDGFRA D842V Mutation
Hide Arm/Group Description:
Patients with a PDGFRA D842V Mutation, any line of treatment
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame For each patient adverse event data were collected starting at the time of the first dose of study drug until 30 days after the final dose of study drug. Serious adverse event data were collected from the time the informed consent was signed until 30 days after the final dose of study drug. On average 8 months, up to 5 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 or 400 mg QD
Hide Arm/Group Description

Part 1: Patients received a starting dose of 30 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 60 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 90 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 135 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 200 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1: Patients received a starting dose of 600 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

Part 1 and Part 2: Patients enrolled in Part 1 and Part 2 at a starting dose of 300 or 400 mg QD were included in the Part1/Part 2 safety and efficacy analysis.

Patients received avapritinib in continuous 28 day cycles until discontinuation.

All-Cause Mortality
Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 or 400 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   4/6 (66.67%)   2/6 (33.33%)   4/6 (66.67%)   3/6 (50.00%)   1/3 (33.33%)   111/217 (51.15%) 
Hide Serious Adverse Events
Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 or 400 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/6 (50.00%)   4/6 (66.67%)   5/6 (83.33%)   5/6 (83.33%)   5/6 (83.33%)   3/3 (100.00%)   140/217 (64.52%) 
Blood and lymphatic system disorders               
Anemia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  1/3 (33.33%)  24/217 (11.06%) 
Febrile neutropenia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Cardiac disorders               
Myocardial infarction  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/217 (0.46%) 
Angina pectoris  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Angina unstable  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Atrial fibrillation  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Cardiac disorder  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Cardiac failure  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Pericardial effusion  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/217 (0.00%) 
Ear and labyrinth disorders               
Vertigo  1  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/217 (0.00%) 
Endocrine disorders               
Adrenal haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Eye disorders               
Papilloedema  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Gastrointestinal disorders               
Abdominal pain  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  8/217 (3.69%) 
Upper gastrointestinal haemorrhage  1  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  4/217 (1.84%) 
Gastrointestinal haemorrhage  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  3/217 (1.38%) 
Vomiting  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  4/217 (1.84%) 
Diarrhoea  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  3/217 (1.38%) 
Ascites  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  3/217 (1.38%) 
Melaena  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  3/217 (1.38%) 
Nausea  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  2/217 (0.92%) 
Peritoneal haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  3/217 (1.38%) 
Small intestinal haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  3/217 (1.38%) 
Small intestinal obstruction  1  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Colitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Gastric haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Intestinal obstruction  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Intra-abdominal haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Lower gastrointestinal haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Rectal haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Subileus  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Enteritis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Enterocolitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Faecaloma  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Gastroduodenal haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Gastrointestinal ulcer haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Ileus  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Intestinal fistula  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Large intestinal obstruction  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Oesophagitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Oesophagitis ulcerative  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
General disorders               
Disease progression  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  18/217 (8.29%) 
General physical health deterioration  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  6/217 (2.76%) 
Fatigue  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Malaise  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Pyrexia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Asthenia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Cyst rupture  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Face oedema  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/217 (0.00%) 
Haemorrhagic cyst  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Hypothermia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Oedema peripheral  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/217 (0.00%) 
Hepatobiliary disorders               
Cholecystitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Cholecystitis acute  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Hepatic failure  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/217 (0.00%) 
Hepatocellular injury  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Hyperbilirubinaemia  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/217 (0.00%) 
Infections and infestations               
Sepsis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  8/217 (3.69%) 
Pneumonia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  7/217 (3.23%) 
Gastroenteritis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Urinary tract infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  3/217 (1.38%) 
Clostridium difficile infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  0/217 (0.00%) 
Device related infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Upper respiratory tract infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Abdominal abscess  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Appendicitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Catheter site infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Cellulitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Clostridium difficile colitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Cystitis  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/217 (0.00%) 
Gastroenteritis viral  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/217 (0.00%) 
Herpes simplex encephalitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Herpes zoster  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Infected cyst  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/217 (0.00%) 
Peritonitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Pneumococcal sepsis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Pneumonia escherichia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Pseudomembranous colitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Pulmonary sepsis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Skin infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/217 (0.00%) 
Spinal cord infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Staphylococcal bacteraemia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Streptococcal infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Wound infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Injury, poisoning and procedural complications               
Subdural haematoma  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Cervical vertebral fracture  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Femur fracture  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Forearm fracture  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Hip fracture  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/217 (0.00%) 
Wound dehiscence  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Investigations               
Blood creatine phosphokinase increased  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Metabolism and nutrition disorders               
Dehydration  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  3/217 (1.38%) 
Hypoglycaemia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Diabetic ketoacidosis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Fluid overload  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Hypomagnesaemia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Hyponatraemia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Malnutrition  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Musculoskeletal and connective tissue disorders               
Fistula discharge  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Muscular weakness  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Pain in extremity  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Tumour haemorrhage  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  4/217 (1.84%) 
Tumour rupture  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Benign gastric neoplasm  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Breast cancer  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Leiomyosarcoma  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Metastases to perineum  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Metastases to peritoneum  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Metastatic neoplasm  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/217 (0.00%) 
Oesophageal squamous cell carcinoma  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/217 (0.00%) 
Prostate cancer  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/217 (0.00%) 
Renal cell carcinoma  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Nervous system disorders               
Cerebral haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Cognitive disorder  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Encephalopathy  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  3/217 (1.38%) 
Transient ischaemic attack  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  3/217 (1.38%) 
Dementia  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Haemorrhage intracranial  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Central nervous system lesion  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Dementia with Lewy bodies  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Dyskinesia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Epilepsy  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/217 (0.00%) 
Headache  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Hepatic encephalopathy  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Nervous system disorder  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Neurological decompensation  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Peroneal nerve palsy  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Somnolence  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Syncope  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/217 (0.00%) 
Psychiatric disorders               
Confusional state  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  3/217 (1.38%) 
Delirium  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Psychotic disorder  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Agitation  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Major depression  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/217 (0.00%) 
Mental disorder  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Mental status changes  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Mood altered  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/217 (0.00%) 
Personality change  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Schizophrenia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Renal and urinary disorders               
Acute kidney injury  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  4/217 (1.84%) 
Hydronephrosis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Nephrolithiasis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Renal failure  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Urinary retention  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Reproductive system and breast disorders               
Pelvic pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Prostatitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/217 (0.00%) 
Testicular pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Respiratory, thoracic and mediastinal disorders               
Pleural effusion  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  5/217 (2.30%) 
Dyspnoea  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Hypoxia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  0/217 (0.00%) 
Pneumonia aspiration  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/217 (0.92%) 
Bronchospasm  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Chronic obstructive pulmonary disease  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Haemothorax  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Laryngeal oedema  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Lung disorder  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Pulmonary embolism  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Respiratory failure  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Restrictive pulmonary disease  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Skin and subcutaneous tissue disorders               
Angioedema  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Circumoral oedema  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
Dermatitis acneiform  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/217 (0.00%) 
Vascular disorders               
Hypertension  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/217 (0.00%) 
Peripheral arterial occlusive disease  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/217 (0.46%) 
1
Term from vocabulary, MedRA
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 or 400 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   6/6 (100.00%)   5/6 (83.33%)   6/6 (100.00%)   6/6 (100.00%)   3/3 (100.00%)   214/217 (98.62%) 
Blood and lymphatic system disorders               
Neutropenia  1  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  24/217 (11.06%) 
Leukopenia  1  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  16/217 (7.37%) 
Lymphopenia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  14/217 (6.45%) 
Eye disorders               
Periorbital oedema  1  4/6 (66.67%)  4/6 (66.67%)  1/6 (16.67%)  4/6 (66.67%)  2/6 (33.33%)  1/3 (33.33%)  95/217 (43.78%) 
Lacrimation increased  1  2/6 (33.33%)  2/6 (33.33%)  2/6 (33.33%)  4/6 (66.67%)  2/6 (33.33%)  1/3 (33.33%)  76/217 (35.02%) 
Eyelid oedema  1  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  18/217 (8.29%) 
Vision blurred  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  14/217 (6.45%) 
Gastrointestinal disorders               
Constipation  1  2/6 (33.33%)  3/6 (50.00%)  2/6 (33.33%)  1/6 (16.67%)  2/6 (33.33%)  1/3 (33.33%)  54/217 (24.88%) 
Dyspepsia  1  2/6 (33.33%)  2/6 (33.33%)  0/6 (0.00%)  4/6 (66.67%)  0/6 (0.00%)  1/3 (33.33%)  36/217 (16.59%) 
Gastrooesophageal reflux disease  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  22/217 (10.14%) 
Abdominal distension  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  22/217 (10.14%) 
Abdominal pain upper  1  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  18/217 (8.29%) 
Dry mouth  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  2/6 (33.33%)  1/3 (33.33%)  16/217 (7.37%) 
Dysphagia  1  2/6 (33.33%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  11/217 (5.07%) 
General disorders               
Feeling cold  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  17/217 (7.83%) 
Influenza like illness  1  1/6 (16.67%)  0/6 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  1/6 (16.67%)  1/3 (33.33%)  11/217 (5.07%) 
Chills  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  12/217 (5.53%) 
Injury, poisoning and procedural complications               
Contusion  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  10/217 (4.61%) 
Investigations               
Blood bilirubin increased  1  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  2/3 (66.67%)  48/217 (22.12%) 
Weight decreased  1  1/6 (16.67%)  2/6 (33.33%)  0/6 (0.00%)  3/6 (50.00%)  1/6 (16.67%)  2/3 (66.67%)  38/217 (17.51%) 
Aspartate aminotransferase increased  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  35/217 (16.13%) 
Blood creatinine increased  1  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  21/217 (9.68%) 
Weight increased  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  15/217 (6.91%) 
Alanine aminotransferase increased  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  13/217 (5.99%) 
Neutrophil count decreased  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  14/217 (6.45%) 
White blood cell count decreased  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  14/217 (6.45%) 
Metabolism and nutrition disorders               
Hypokalaemia  1  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  1/3 (33.33%)  43/217 (19.82%) 
Hypophosphataemia  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  3/6 (50.00%)  2/6 (33.33%)  1/3 (33.33%)  34/217 (15.67%) 
Decreased appetite  1  1/6 (16.67%)  3/6 (50.00%)  2/6 (33.33%)  3/6 (50.00%)  2/6 (33.33%)  3/3 (100.00%)  88/217 (40.55%) 
Musculoskeletal and connective tissue disorders               
Back pain  1  1/6 (16.67%)  0/6 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  1/6 (16.67%)  1/3 (33.33%)  25/217 (11.52%) 
Myalgia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  1/3 (33.33%)  15/217 (6.91%) 
Arthralgia  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  14/217 (6.45%) 
Nervous system disorders               
Memory impairment  1  2/6 (33.33%)  2/6 (33.33%)  0/6 (0.00%)  2/6 (33.33%)  2/6 (33.33%)  1/3 (33.33%)  73/217 (33.64%) 
Dizziness  1  2/6 (33.33%)  1/6 (16.67%)  0/6 (0.00%)  2/6 (33.33%)  2/6 (33.33%)  2/3 (66.67%)  51/217 (23.50%) 
Dysgeusia  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  3/6 (50.00%)  1/6 (16.67%)  2/3 (66.67%)  40/217 (18.43%) 
Disturbance in attention  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  16/217 (7.37%) 
Peripheral sensory neuropathy  1  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  1/3 (33.33%)  13/217 (5.99%) 
Paraesthesia  1  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  2/6 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  11/217 (5.07%) 
Psychiatric disorders               
Insomnia  1  2/6 (33.33%)  2/6 (33.33%)  0/6 (0.00%)  3/6 (50.00%)  1/6 (16.67%)  1/3 (33.33%)  32/217 (14.75%) 
Anxiety  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  1/3 (33.33%)  20/217 (9.22%) 
Depression  1  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  2/6 (33.33%)  2/6 (33.33%)  0/3 (0.00%)  11/217 (5.07%) 
Respiratory, thoracic and mediastinal disorders               
Cough  1  2/6 (33.33%)  1/6 (16.67%)  4/6 (66.67%)  0/6 (0.00%)  4/6 (66.67%)  2/3 (66.67%)  27/217 (12.44%) 
Skin and subcutaneous tissue disorders               
Hair colour changes  1  2/6 (33.33%)  2/6 (33.33%)  1/6 (16.67%)  4/6 (66.67%)  2/6 (33.33%)  1/3 (33.33%)  50/217 (23.04%) 
Alopecia  1  1/6 (16.67%)  2/6 (33.33%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/3 (33.33%)  31/217 (14.29%) 
Rash  1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  2/6 (33.33%)  1/3 (33.33%)  30/217 (13.82%) 
Dry skin  1  2/6 (33.33%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  21/217 (9.68%) 
Pruritus  1  3/6 (50.00%)  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  18/217 (8.29%) 
Rash maculo-papular  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  13/217 (5.99%) 
1
Term from vocabulary, MedRA
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Information
Organization: Blueprint Medicines
Phone: 1-888-258-7768
EMail: medinfo@blueprintmedicines.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Blueprint Medicines Corporation
ClinicalTrials.gov Identifier: NCT02508532    
Other Study ID Numbers: BLU-285-1101
First Submitted: July 23, 2015
First Posted: July 27, 2015
Results First Submitted: March 5, 2021
Results First Posted: June 22, 2021
Last Update Posted: July 2, 2021