(NAVIGATOR) Study of BLU-285 in Patients With Gastrointes... | NCT02508532 | Trialant
NCT02508532
Sponsor
Blueprint Medicines Corporation
Status
Completed
Last Update Posted
Jun 21, 2022Actual
Enrollment
250Actual
Phase
Phase 1
Conditions
Gastrointestinal Stromal Tumors (GIST)
Other Relapsed or Refractory Solid Tumors
Interventions
Avapritinib
Countries
United States
Belgium
France
Germany
Italy
Netherlands
Poland
South Korea
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02508532
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
BLU-285-1101
Secondary IDs
Not provided
Brief Title
(NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors
Official Title
A Phase 1 Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors
Acronym
Not provided
Organization
Blueprint Medicines CorporationINDUSTRY
Status Module
Record Verification Date
Jul 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
YesNCT03862885Approved for marketing
Start Date
Aug 2015Actual
Primary Completion Date
Mar 6, 2020Actual
Completion Date
Jun 3, 2021Actual
First Submitted Date
Jul 23, 2015
First Submission Date that Met QC Criteria
Jul 23, 2015
First Posted Date
Jul 27, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Mar 5, 2021
Results First Submitted that Met QC Criteria
May 27, 2021
Results First Posted Date
Jun 22, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 20, 2022
Last Update Posted Date
Jun 21, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Blueprint Medicines CorporationINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of avapritinib (formerly BLU-285), administered orally (PO), in adult patients with unresectable GIST or other relapsed or refractory solid tumors. The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 2).
Detailed Description
Not provided
Conditions Module
Conditions
Gastrointestinal Stromal Tumors (GIST)
Other Relapsed or Refractory Solid Tumors
Keywords
2L GIST
GIST second line
GIST gleevec
GIST imatinib
Second-line GIST clinical trial
BLU-285
BLU 285
BLUE-285
BLUE 285
Avapritinib
GIST imatinib relapse
GIST gleevec relapse
GIST KIT
GIST relapse
GIST refractory
GIST imatinib intolerance
GIST TKI treatment
GIST tyrosine kinase inhibitor treatment
GIST TKI
GIST tyrosine kinase inhibitor
Advanced GIST
GIST mutations
GIST treatments
Blueprint GIST
Relapsed GIST clinical trial
Refractory GIST clinical trial
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
250Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part 1 Avapritinib (formerly BLU-285) 30 mg QD
Experimental
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.
Drug: Avapritinib
Part 1 Avapritinib (formerly BLU-285) 60 mg QD
Experimental
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.
Drug: Avapritinib
Part 1 Avapritinib (formerly BLU-285) 90 mg QD
Experimental
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.
Drug: Avapritinib
Part 1 Avapritinib (formerly BLU-285) 135 mg QD
Experimental
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.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Avapritinib
Drug
avapritinib tablets
Part 1 Avapritinib (formerly BLU-285) 135 mg QD
Part 1 Avapritinib (formerly BLU-285) 200 mg QD
Part 1 Avapritinib (formerly BLU-285) 30 mg QD
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib
Patients with event(s) of dose-limiting toxicity
Cycle 1 (28 days) of treatment
Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE)
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.
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
Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1
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
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.
Secondary Outcomes
Measure
Description
Time Frame
Maximum Plasma Drug Concentration (Cmax)
Maximum plasma drug concentration (Cmax) following a single dose of avapritinib
Cycle 1 Day 1
Time to Maximum Plasma Drug Concentration (Tmax)
Cycle 1 Day 1 PK time to maximum plasma drug concentration (Tmax)
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
For Part 1: Histologically- or cytologically-confirmed diagnosis of unresectable GIST or another advanced solid tumor. Patients with unresectable GIST must have disease that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib or an experimental kinase-inhibitor agent, or disease with a D842 mutation in the PDGFRα gene. Patients with an advanced solid tumor other than GIST must have relapsed or refractory disease without an available effective therapy.
OR For Part 2:
Group 1: Patients must have a confirmed diagnosis of unresectable GIST that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib, or an experimental kinase-inhibitor agent, and the patient does not have a D842V mutation in PDGFRα.
Group 2: Patients must have a confirmed diagnosis of unresectable GIST with a D842V mutation in the PDGFRα gene. The PDGFRα mutation will be identified by local or central assessment, either in an archival tissue sample or a new tumor biopsy obtained prior to treatment with avapritinib.
Group 3: Patients must have a confirmed diagnosis of unresectable GIST that has progressed and/or patients must have experienced intolerance to imatinib and not received additional kinase-inhibitor therapy. Patients must not have a known D842V mutation in PDGFRα.
Groups 1, 2 and 3: At least 1 measurable lesion defined by mRECIST 1.1 for patients with GIST.
Groups 1 and 2: A tumor sample (archival tissue or a new tumor biopsy) has been submitted for mutational testing.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Exclusion Criteria:
QT interval corrected using Fridericia's formula (QTcF) >450 milliseconds
Platelet count <90,000/mL
Absolute neutrophil count <1000/mL
Hemoglobin <9 g/dL
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 x the upper limit of normal (ULN) if no hepatic metastases are present; >5 × ULN if hepatic metastases are present
Total bilirubin >1.5 × ULN; >3 × ULN with direct bilirubin, >1.5 × ULN in the presence of Gilbert's Disease
Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min Brain malignancy or metastases to the brain
History of a seizure disorder or requirement for anti-seizure medication
Kang YK, George S, Jones RL, Rutkowski P, Shen L, Mir O, Patel S, Zhou Y, von Mehren M, Hohenberger P, Villalobos V, Brahmi M, Tap WD, Trent J, Pantaleo MA, Schoffski P, He K, Hew P, Newberry K, Roche M, Heinrich MC, Bauer S. Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study. J Clin Oncol. 2021 Oct 1;39(28):3128-3139. doi: 10.1200/JCO.21.00217. Epub 2021 Aug 3.
Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD
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.
FG001
Periods
Title
Milestones
Reasons Not Completed
Part 1 - Dose Determining Period
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Feb 28, 2018
Mar 5, 2021
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
KIT-mutant GIST
cancer gist
gastrointestinal stromal tumor
gist cancer
PDGFRA
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Dose Escalation and Dose Expansion
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug: Avapritinib
Part 1 Avapritinib (formerly BLU-285) 200 mg QD
Experimental
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. .
Drug: Avapritinib
Part 1 Avapritinib (formerly BLU-285) 300 mg QD
Experimental
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.
Drug: Avapritinib
Part 1 Avapritinib (formerly BLU-285) 400 mg QD
Experimental
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.
Drug: Avapritinib
Part 1 Avapritinib (formerly BLU-285) 600 mg QD
Experimental
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.
Drug: Avapritinib
Part 1 and Part 2 Avapritinib (formerly BLU-285) 300 mg or 400 mg QD
Experimental
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.
Drug: Avapritinib
Part 1 Avapritinib (formerly BLU-285) 300 mg QD
Part 1 Avapritinib (formerly BLU-285) 400 mg QD
Part 1 Avapritinib (formerly BLU-285) 60 mg QD
Part 1 Avapritinib (formerly BLU-285) 600 mg QD
Part 1 Avapritinib (formerly BLU-285) 90 mg QD
Part 1 and Part 2 Avapritinib (formerly BLU-285) 300 mg or 400 mg QD
BLU-285
Cycle 1 Day 1
Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose (C24)
Plasma drug concentration at 24 hours postdose prior to the next daily dose (C24) following a single dose of avapritinib
Cycle 1 Day 1
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC 0-24)
Area under the plasma concentration-time curve from time 0 to 24 hours (AUC 0-24) following a single dose of avapritinib
Cycle 1 Day 1
Apparent Oral Clearance Unadjusted for Bioavailability (CL/F)
Apparent oral clearance unadjusted for bioavailability (CL/F) following a single dose of avapritinib
Cycle 1 Day 1
Apparent Volume of Distribution, Unadjusted for Bioavailability (Vz/F)
Apparent volume of distribution, unadjusted for bioavailability (Vz/F) following a single dose of avapritinib
Cycle 1 Day 1
Terminal Elimination Half-life (t1/2)
Terminal elimination half-life (t1/2) following a single dose of avapritinib
Cycle 1 Day 1
Maximum Plasma Drug Concentration (Cmax) at Steady State
Maximum plasma drug concentration (Cmax) at steady state following 15 days of QD dosing
Cycle 1 Day 15
Time of Maximal Concentration (Tmax) at Steady State
Time of maximal concentration (Tmax) at steady state following 15 days of QD dosing
Cycle 1 Day 15
Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at Steady State (C24,ss)
Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at steady state (C24,ss) following 15 days of QD dosing
Cycle 1 Day 15
Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady Sate (AUC0-Ï„,ss) (Ï„=24 h)
Area under the plasma concentration-time curve over the dosing interval at steady sate (AUC0-Ï„,ss) (Ï„=24 h) following 15 days of QD dosing
Cycle 1 Day 15
Progression-free Survival Per mRECIST Version 1.1
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.
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.
Apparent Oral Clearance at Steady State, Unadjusted for Bioavailability (CLss/F)
Apparent oral clearance at steady state, unadjusted for bioavailability (CLss/F) following 15 days of QD dosing
Cycle 1 Day 15
Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1
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.
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.
Response Rate Determined by Central Radiology Assessment Per Choi Criteria
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.
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.
Duration of Response Determined by Central Radiology Assessment Per mRECIST, Version 1.1
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
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.
Median PFS on Last Prior Anti-cancer Therapy
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.
Historical data collected at enrollment, all available data on prior therapy was collected
Change From Baseline in Levels of KIT and PDGFRα Mutant Allele Fractions in Peripheral Blood
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.
Baseline and End of treatment
KIT, PDGFRA, and Other Cancer-relevant Mutations Present in Tumor Tissue at Baseline and EOT
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.
Baseline and end of treatment
Santa Monica
California
90403
United States
Sylvester Comprehensive Cancer Center
Miami
Florida
33136
United States
Cancer Treatment Centers of America
Atlanta
Georgia
30256
United States
Dana Farber Cancer Institute
Boston
Massachusetts
02215
United States
Memorial Sloan Kettering Cancer Center
New York
New York
10065
United States
Oregon Health and Science University
Portland
Oregon
97239
United States
Fox Chase Cancer Center
Philadelphia
Pennsylvania
19111
United States
MD Anderson Cancer Center
Houston
Texas
77030
United States
Leuven Cancer Institute University Hospitals Leuven
Leuven
3000
Belgium
Centre Leon Berard
Lyon
69008
France
Institut Gustave Roussy
Paris
94805
France
University of Duisburg-Essen
Essen
45122
Germany
Fondazione IRCCS - Istituto Nazinale dei Tumori
Milan
20133
Italy
Erasmus MC Cancer Institute
Rotterdam
3015
Netherlands
Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie w Warszawie
Warsaw
02-781
Poland
Asan Medical Center
Seoul
05505
South Korea
Vall d' Hebron Institute of Oncology (VHIO)
Barcelona
08305
Spain
Royal Marsden Hospital
London
SW3 6JJ
United Kingdom
Derived
von Mehren M, Heinrich MC, Shi H, Iannazzo S, Mankoski R, Dimitrijevic S, Hoehn G, Chiroli S, George S. Clinical efficacy comparison of avapritinib with other tyrosine kinase inhibitors in gastrointestinal stromal tumors with PDGFRA D842V mutation: a retrospective analysis of clinical trial and real-world data. BMC Cancer. 2021 Mar 19;21(1):291. doi: 10.1186/s12885-021-08013-1.
Jones RL, Serrano C, von Mehren M, George S, Heinrich MC, Kang YK, Schoffski P, Cassier PA, Mir O, Chawla SP, Eskens FALM, Rutkowski P, Tap WD, Zhou T, Roche M, Bauer S. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021 Mar;145:132-142. doi: 10.1016/j.ejca.2020.12.008. Epub 2021 Jan 16.
Heinrich MC, Jones RL, von Mehren M, Schoffski P, Serrano C, Kang YK, Cassier PA, Mir O, Eskens F, Tap WD, Rutkowski P, Chawla SP, Trent J, Tugnait M, Evans EK, Lauz T, Zhou T, Roche M, Wolf BB, Bauer S, George S. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020 Jul;21(7):935-946. doi: 10.1016/S1470-2045(20)30269-2.
Gebreyohannes YK, Wozniak A, Zhai ME, Wellens J, Cornillie J, Vanleeuw U, Evans E, Gardino AK, Lengauer C, Debiec-Rychter M, Sciot R, Schoffski P. Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal Tumors. Clin Cancer Res. 2019 Jan 15;25(2):609-618. doi: 10.1158/1078-0432.CCR-18-1858. Epub 2018 Oct 1.
Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD
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.
FG002
Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD
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.
FG003
Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD
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.
FG004
Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD
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. .
FG005
Experimental: Part 1 Avapritinib (Formerly BLU-285) 300 mg QD
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.
FG006
Experimental: Part 1 Avapritinib (Formerly BLU-285) 400 mg QD
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.
FG007
Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD
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.
FG008
Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 or 400 mg QD
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.
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG0046 subjects
FG0056 subjects
FG0067 subjects
FG0073 subjects
FG0080 subjectsThis 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
Patients From Part 1 Included in the Part 2 Analyses
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0056 subjects
FG0067 subjects
FG0070 subjects
FG0080 subjects
COMPLETED
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG0046 subjects
FG0056 subjects
FG0066 subjects
FG0072 subjects
FG0080 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0061 subjects
FG0071 subjects
FG0080 subjects
Type
Comment
Reasons
did not complete >21 days of treatment
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0061 subjects
FG0070 subjects
FG0080 subjects
Not Evaluable
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Part 2 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThese patients are not included in Part 2 analyses
FG0010 subjectsThese patients are not included in Part 2 analyses
FG0020 subjectsThese patients are not included in Part 2 analyses
FG0030 subjectsThese patients are not included in Part 2 analyses
FG0040 subjectsThese patients are not included in Part 2 analyses
FG0050 subjectsPart 1 Only:
6 Patients from this group are included in the 300 or 400 mg QD group.
FG0060 subjectsPart 1 Only:
7 Patients from this group are included in the 300 or 400 mg QD group.
FG0070 subjectsThese patients are not included in Part 2 analyses
FG008217 subjectsIncludes 13 patients enrolled in Part 1 at a starting dose of 300 mg (n = 6) or 400 mg (n = 7) QD.
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Disease Progression
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part 1 and Part 2 End of Study
Type
Comment
Milestone Data
STARTED
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG0046 subjects
FG0050 subjectsThese 6 patients are included in the 300 or 400 mg QD dose group
FG0060 subjectsThese 7 patients are included in the 300 or 400 mg QD dose group
FG0073 subjects
FG008217 subjectsIncludes 13 patients enrolled in Part 1 at a starting dose of 300 mg (n = 6) or 400 mg (n = 7) QD.
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG004
Type
Comment
Reasons
Disease Progression
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD
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.
BG001
Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD
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.
BG002
Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD
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.
BG003
Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD
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.
BG004
Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD
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. .
BG005
Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD
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.
BG006
Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 mg or 400 mg QD
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
BG007
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0006
BG0016
BG0026
BG0036
BG0046
BG0053
BG006217
BG007250
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG0006
ParticipantsBG0016
ParticipantsBG0026
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0006
ParticipantsBG0016
ParticipantsBG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0006
ParticipantsBG0016
ParticipantsBG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
Belgium
ParticipantsBG0006
ParticipantsBG0016
ParticipantsBG002
Body Mass Index (BMI)
Body Mass Index was only calculated for patients with both a height and weight measurement at Baseline
Mean
Standard Deviation
kg/m2
Title
Denominators
Categories
ParticipantsBG0003
ParticipantsBG0016
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib
Patients with event(s) of dose-limiting toxicity
Patients that completed Part 1 or had a DLT
Posted
Number
patients with event(s) of dose-limiting
Cycle 1 (28 days) of treatment
ID
Title
Description
OG000
Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD
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.
OG001
Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD
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.
OG002
Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD
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.
OG003
Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD
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.
OG004
Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD
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. .
OG005
Experimental: Part 1 Avapritinib (Formerly BLU-285) 300 mg QD
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.
OG006
Experimental: Part 1 Avapritinib (Formerly BLU-285) 400 mg QD
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.
OG007
Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD
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.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE)
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.
Safety Population - all patients that received at least one dose of avapritinib
Posted
Number
participants
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
ID
Title
Description
OG000
Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD
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.
OG001
Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD
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.
OG002
Primary
Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1
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
patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg, including 13 patients enrolled in Part 1
Posted
Count of Participants
Participants
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.
ID
Title
Description
OG000
Patients With a PDGFRA D842V Mutation
Patients with a PDGFRA D842V Mutation, any line of treatment
OG001
2L Patients Without a PDGFRA D842V Mutation
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
OG002
3L Patients Without a PDGFRA D842V Mutation
Secondary
Maximum Plasma Drug Concentration (Cmax)
Maximum plasma drug concentration (Cmax) following a single dose of avapritinib
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Posted
Median
Standard Deviation
ng/mL
Cycle 1 Day 1
ID
Title
Description
OG000
Part 1 Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Time to Maximum Plasma Drug Concentration (Tmax)
Cycle 1 Day 1 PK time to maximum plasma drug concentration (Tmax)
Patients enrolled in Part 1 and Part 2 with available samples for PK
Posted
Median
Full Range
hours
Cycle 1 Day 1
ID
Title
Description
OG000
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose (C24)
Plasma drug concentration at 24 hours postdose prior to the next daily dose (C24) following a single dose of avapritinib
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 1
ID
Title
Description
OG000
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC 0-24)
Area under the plasma concentration-time curve from time 0 to 24 hours (AUC 0-24) following a single dose of avapritinib
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
Posted
Mean
Standard Deviation
h*ng/mL
Cycle 1 Day 1
ID
Title
Description
OG000
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Apparent Oral Clearance Unadjusted for Bioavailability (CL/F)
Apparent oral clearance unadjusted for bioavailability (CL/F) following a single dose of avapritinib
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
Posted
Mean
Standard Deviation
L/h
Cycle 1 Day 1
ID
Title
Description
OG000
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Apparent Volume of Distribution, Unadjusted for Bioavailability (Vz/F)
Apparent volume of distribution, unadjusted for bioavailability (Vz/F) following a single dose of avapritinib
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
Posted
Mean
Standard Error
L
Cycle 1 Day 1
ID
Title
Description
OG000
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Terminal Elimination Half-life (t1/2)
Terminal elimination half-life (t1/2) following a single dose of avapritinib
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
Posted
Mean
Standard Deviation
h
Cycle 1 Day 1
ID
Title
Description
OG000
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Maximum Plasma Drug Concentration (Cmax) at Steady State
Maximum plasma drug concentration (Cmax) at steady state following 15 days of QD dosing
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 15
ID
Title
Description
OG000
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Time of Maximal Concentration (Tmax) at Steady State
Time of maximal concentration (Tmax) at steady state following 15 days of QD dosing
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Posted
Median
Full Range
h
Cycle 1 Day 15
ID
Title
Description
OG000
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at Steady State (C24,ss)
Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at steady state (C24,ss) following 15 days of QD dosing
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 15
ID
Title
Description
OG000
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady Sate (AUC0-Ï„,ss) (Ï„=24 h)
Area under the plasma concentration-time curve over the dosing interval at steady sate (AUC0-Ï„,ss) (Ï„=24 h) following 15 days of QD dosing
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Posted
Mean
Standard Deviation
h*ng/mL
Cycle 1 Day 15
ID
Title
Description
OG000
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Progression-free Survival Per mRECIST Version 1.1
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.
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD
Posted
Median
95% Confidence Interval
months
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.
ID
Title
Description
OG000
Patients With a PDGFRA D842V Mutation
Patients with a PDGFRA D842V mutation, any line of treatment
OG001
2L Patients Without a PDGFRA D842V Mutation
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
OG002
3L Patients Without a PDGFRA D842V Mutation
Secondary
Apparent Oral Clearance at Steady State, Unadjusted for Bioavailability (CLss/F)
Apparent oral clearance at steady state, unadjusted for bioavailability (CLss/F) following 15 days of QD dosing
Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
Posted
Mean
Standard Deviation
L/h
Cycle 1 Day 15
ID
Title
Description
OG000
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 300 mg QD
Part 1 and Part 2: Patients received a starting dose of 300 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
OG001
Part 1 and Part 2: Avapritinib (Formerly BLU-285) 400 mg QD
Part 1 and Part 2: Patients received a starting dose of 400 mg QD. Patients received avapritinib in continuous 28 day cycles until discontinuation.
Units
Counts
Participants
OG000
Secondary
Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1
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.
patients with a starting dose of 300 or 400 mg QD
Posted
Count of Participants
Participants
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.
ID
Title
Description
OG000
Patients With a PDGFRA D842V Mutation
Patients with a PDGFRA D842V mutation, any line of treatment
OG001
2L Patients Without a PDGFRA D842V Mutation
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
Secondary
Response Rate Determined by Central Radiology Assessment Per Choi Criteria
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.
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg
Posted
Count of Participants
Participants
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.
ID
Title
Description
OG000
Patients With a PDGFRA D842V Mutation
Patients with a PDGFRA D842V mutation, any line of treatment
OG001
2L Patients Without a PDGFRA D842V Mutation
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
OG002
3L Patients Without a PDGFRA D842V Mutation
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Secondary
Duration of Response Determined by Central Radiology Assessment Per mRECIST, Version 1.1
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
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
Posted
Median
95% Confidence Interval
months
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.
ID
Title
Description
OG000
Patients With PDGFRA D842V Mutation
Patients with a PDGFRA D842V mutation, any line of treatment
OG001
2L Patients Without a PDGFRA D842V Mutation
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
OG002
3L Patients Without a PDGFRA D842V Mutation
Secondary
Median PFS on Last Prior Anti-cancer Therapy
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.
Patients enrolled on any dose (Part 1 and Part 2) with data on progression-free survival for the most recent prior therapy
Posted
Median
95% Confidence Interval
months
Historical data collected at enrollment, all available data on prior therapy was collected
ID
Title
Description
OG000
Patients With a PDGFRA D842V Mutation
Patients with a PDGFRA D842V mutation, any line of treatment
OG001
2L Patients Without a PDGFRA D842V Mutation
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
OG002
3L Patients Without a PDGFRA D842V Mutation
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Secondary
Change From Baseline in Levels of KIT and PDGFRα Mutant Allele Fractions in Peripheral Blood
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.
Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD
Posted
Mean
Standard Deviation
fraction of total
Baseline and End of treatment
ID
Title
Description
OG000
Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 mg or 400 mg QD
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.
Units
Counts
Participants
OG000
Secondary
KIT, PDGFRA, and Other Cancer-relevant Mutations Present in Tumor Tissue at Baseline and EOT
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.
Patients with pre-and post-treatment tumor biopsies. No patients provided a post-treatment biopsy.
Posted
Baseline and end of treatment
ID
Title
Description
OG000
Patients With a PDGFRA D842V Mutation
Patients with a PDGFRA D842V Mutation, any line of treatment
OG001
2L Patients Without a PDGFRA D842V Mutation
Patients that do not have a PDGFRA D842V mutation and have received 1 prior line of therapy
OG002
3L Patients Without a PDGFRA D842V Mutation
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Units
Counts
Participants
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.
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD
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.
0
6
3
6
6
6
EG001
Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD
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.
4
6
4
6
6
6
EG002
Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD
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.
2
6
5
6
5
6
EG003
Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD
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.
4
6
5
6
6
6
EG004
Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD
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.
3
6
5
6
6
6
EG005
Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD
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.
1
3
3
3
3
3
EG006
Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 or 400 mg QD
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.
111
217
140
217
214
217
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anemia
Blood and lymphatic system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG0031 affected6 at risk
EG0041 affected6 at risk
EG0051 affected3 at risk
EG00624 affected217 at risk
Febrile neutropenia
Blood and lymphatic system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected6 at risk
EG0020 affected6 at risk
EG003
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0001 affected6 at risk
EG0011 affected6 at risk
EG0020 affected6 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Vomiting
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Ascites
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Melaena
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Nausea
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Peritoneal haemorrhage
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Small intestinal haemorrhage
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0001 affected6 at risk
EG0011 affected6 at risk
EG0020 affected6 at risk
EG003
Colitis
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Gastric haemorrhage
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Intestinal obstruction
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Intra-abdominal haemorrhage
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Lower gastrointestinal haemorrhage
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Subileus
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Enteritis
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Enterocolitis
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Faecaloma
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Gastroduodenal haemorrhage
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Gastrointestinal ulcer haemorrhage
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Ileus
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Intestinal fistula
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Large intestinal obstruction
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Oesophagitis
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Oesophagitis ulcerative
Gastrointestinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Sepsis
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Pneumonia
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Gastroenteritis
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Urinary tract infection
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Clostridium difficile infection
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Device related infection
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Abdominal abscess
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Appendicitis
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Catheter site infection
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Cellulitis
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Cystitis
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected6 at risk
EG0020 affected6 at risk
EG003
Herpes simplex encephalitis
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Herpes zoster
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Infected cyst
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Peritonitis
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Pneumococcal sepsis
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Pneumonia escherichia
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Pseudomembranous colitis
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Pulmonary sepsis
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Skin infection
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Spinal cord infection
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Staphylococcal bacteraemia
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Streptococcal infection
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Wound infection
Infections and infestations
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Disease progression
General disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
General physical health deterioration
General disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected6 at risk
EG0020 affected6 at risk
EG003
Fatigue
General disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Malaise
General disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Pyrexia
General disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Asthenia
General disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Cyst rupture
General disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Face oedema
General disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Haemorrhagic cyst
General disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Hypothermia
General disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Oedema peripheral
General disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Cerebral haemorrhage
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
Cognitive disorder
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Encephalopathy
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Dementia
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
Haemorrhage intracranial
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Central nervous system lesion
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Dementia with Lewy bodies
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Dyskinesia
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Epilepsy
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
Headache
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Hepatic encephalopathy
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Nervous system disorder
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Neurological decompensation
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Peroneal nerve palsy
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Somnolence
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Syncope
Nervous system disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Pneumonia aspiration
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Bronchospasm
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Chronic obstructive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Haemothorax
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Laryngeal oedema
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Lung disorder
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Restrictive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Tumour haemorrhage
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected6 at risk
EG0020 affected6 at risk
EG003
Tumour rupture
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Benign gastric neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Breast cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Leiomyosarcoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Metastases to perineum
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Metastases to peritoneum
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Metastatic neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
Oesophageal squamous cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
Prostate cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedRA
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Renal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD
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.
OG003
Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD
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.
OG004
Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD
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. .
OG005
Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD
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.
OG006
Experimental: Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 mg or 400 mg QD
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.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0053
OG006217
Title
Denominators
Categories
Participants with an Adverse Event
Title
Measurements
OG0006
OG0016
OG0026
OG0036
OG0046
OG0053
OG006216
Participants with a Serious Adverse Event
Title
Measurements
OG0003
OG0014
OG0025
OG003
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Units
Counts
Participants
OG00038
OG00150
OG002128
Title
Denominators
Categories
Title
Measurements
Responder
OG00036
OG00110
OG00220
Non-Responder
OG0002
OG00140
OG002108
113
OG00150
Title
Denominators
Categories
Title
Measurements
OG000305± 153
OG001343± 181
113
OG00150
Title
Denominators
Categories
Title
Measurements
OG0004.0(0.98 to 23.5)
OG0014.02(1.97 to 24.0)
36
OG00119
Title
Denominators
Categories
Title
Measurements
OG000134± 49.4
OG001185± 80.2
36
OG00119
Title
Denominators
Categories
Title
Measurements
OG0004510± 1760
OG0015310± 2080
23
OG0018
Title
Denominators
Categories
Title
Measurements
OG00031.5± 15.2
OG00129.9± 20.1
23
OG0018
Title
Denominators
Categories
Title
Measurements
OG0001310± 676
OG0011340± 597
23
OG0018
Title
Denominators
Categories
Title
Measurements
OG00032.1± 15.6
OG00143.5± 28.4
110
OG00138
Title
Denominators
Categories
Title
Measurements
OG000905± 402
OG0011140± 469
110
OG00138
Title
Denominators
Categories
Title
Measurements
OG0004.0(0.0 to 8.17)
OG0013.99(0.5 to 8.0)
110
OG00138
Title
Denominators
Categories
Title
Measurements
OG000593± 263
OG001760± 343
110
OG00138
Title
Denominators
Categories
Title
Measurements
OG00016900± 7230
OG00121300± 9250
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Units
Counts
Participants
OG00038
OG00150
OG002128
Title
Denominators
Categories
Title
Measurements
OG00027.6(19.5 to NA)The upper bounds of the confidence interval could not be calculated
OG0015.5(2.0 to 9.4)
OG0023.7(3.6 to 5.6)
110
OG00138
Title
Denominators
Categories
Title
Measurements
OG00021.8± 12.0
OG00122.8± 11.7
OG002
3L Patients Without a PDGFRA D842V Mutation
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Units
Counts
Participants
OG00038
OG00150
OG002128
Title
Denominators
Categories
Title
Measurements
Clinical Benefit
OG00037
OG00126
OG00251
No Clinical Benefit
OG0001
OG00124
OG00277
Units
Counts
Participants
OG00038
OG00150
OG002128
Title
Denominators
Categories
Title
Measurements
Responder
OG00037
OG00118
OG00245
Non-responder
OG0001
OG00132
OG00283
Patients that do not have a PDGFRA D842V mutation and have had 2 or more prior lines of therapy
Units
Counts
Participants
OG00036
OG00110
OG00220
Title
Denominators
Categories
Title
Measurements
OG00022.1(14.3 to NA)The upper bounds of the confidence interval could not be calculated
OG00119.2(9.2 to 19.2)
OG00210.2(7.2 to 15.0)
Units
Counts
Participants
OG00045
OG00151
OG002142
Title
Denominators
Categories
Title
Measurements
OG0005.9(4.2 to 8.3)
OG00131.0(26.4 to 48.0)
OG0026.4(4.3 to 8.3)
1
Title
Denominators
Categories
Change in PDGFRA MAF
Title
Measurements
OG0008.702± NAOnly one patient had data for this outcome measure so the standard deviation cannot be calculated
Change in KIT MAF
Title
Measurements
OG00014.398± NAOnly one patient had data for this outcome measure so the standard deviation cannot be calculated