Gastrointestinal Stromal Tumors (GIST), Other Relapsed or Refractory Solid Tumors
Conditions
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, KIT-mutant GIST, cancer gist, gastrointestinal stromal tumor, gist cancer, PDGFRA
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).
Interventions
DRUGAvapritinib
avapritinib tablets
Sponsors
Blueprint Medicines Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose Escalation and Dose Expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Group 3: Patients known to be KIT wild type.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib | Cycle 1 (28 days) of treatment | Patients with event(s) of dose-limiting toxicity |
| Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | 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 | 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. |
| Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | 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. | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC 0-24) | Cycle 1 Day 1 | Area under the plasma concentration-time curve from time 0 to 24 hours (AUC 0-24) following a single dose of avapritinib |
| Apparent Oral Clearance Unadjusted for Bioavailability (CL/F) | Cycle 1 Day 1 | Apparent oral clearance unadjusted for bioavailability (CL/F) following a single dose of avapritinib |
| Apparent Volume of Distribution, Unadjusted for Bioavailability (Vz/F) | Cycle 1 Day 1 | Apparent volume of distribution, unadjusted for bioavailability (Vz/F) following a single dose of avapritinib |
| Terminal Elimination Half-life (t1/2) | Cycle 1 Day 1 | Terminal elimination half-life (t1/2) following a single dose of avapritinib |
| Maximum Plasma Drug Concentration (Cmax) at Steady State | Cycle 1 Day 15 | Maximum plasma drug concentration (Cmax) at steady state following 15 days of QD dosing |
| Time of Maximal Concentration (Tmax) at Steady State | Cycle 1 Day 15 | Time of maximal concentration (Tmax) at steady state following 15 days of QD dosing |
| Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at Steady State (C24,ss) | Cycle 1 Day 15 | Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at steady state (C24,ss) following 15 days of QD dosing |
| Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady Sate (AUC0-τ,ss) (τ=24 h) | Cycle 1 Day 15 | 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 |
| Maximum Plasma Drug Concentration (Cmax) | Cycle 1 Day 1 | Maximum plasma drug concentration (Cmax) following a single dose of avapritinib |
| Apparent Oral Clearance at Steady State, Unadjusted for Bioavailability (CLss/F) | Cycle 1 Day 15 | Apparent oral clearance at steady state, unadjusted for bioavailability (CLss/F) following 15 days of QD dosing |
| Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | 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. | 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. |
| Response Rate Determined by Central Radiology Assessment Per Choi Criteria | 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. | 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. |
| Duration of Response Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | 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 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 |
| Median PFS on Last Prior Anti-cancer Therapy | Historical data collected at enrollment, all available data on prior therapy was collected | 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. |
| Change From Baseline in Levels of KIT and PDGFRα Mutant Allele Fractions in Peripheral Blood | Baseline and End of treatment | 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. |
| KIT, PDGFRA, and Other Cancer-relevant Mutations Present in Tumor Tissue at Baseline and EOT | Baseline and end of treatment | 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. |
| Progression-free Survival Per mRECIST Version 1.1 | 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. | 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 to Maximum Plasma Drug Concentration (Tmax) | Cycle 1 Day 1 | Cycle 1 Day 1 PK time to maximum plasma drug concentration (Tmax) |
| Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose (C24) | Cycle 1 Day 1 | Plasma drug concentration at 24 hours postdose prior to the next daily dose (C24) following a single dose of avapritinib |
Countries
Belgium, France, Germany, Italy, Netherlands, Poland, South Korea, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. . | 6 |
| 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. | 3 |
| 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 | 217 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 and Part 2 End of Study | Adverse Event | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 |
| Part 1 and Part 2 End of Study | Death | 0 | 4 | 2 | 4 | 3 | 0 | 0 | 1 | 111 |
| Part 1 and Part 2 End of Study | Disease Progression | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 6 |
| Part 1 and Part 2 End of Study | Initiation of another therapy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part 1 and Part 2 End of Study | Lost to Follow-up | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 6 |
| Part 1 and Part 2 End of Study | Physician Decision | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 8 |
| Part 1 and Part 2 End of Study | Sponsor Decision | 2 | 1 | 1 | 2 | 2 | 0 | 0 | 1 | 68 |
| Part 1 and Part 2 End of Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 15 |
| Part 1 - Dose Determining Period | did not complete >21 days of treatment | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1 - Dose Determining Period | Not Evaluable | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 2 - Treatment | Administrative | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Part 2 - Treatment | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 49 |
| Part 2 - Treatment | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part 2 - Treatment | Disease Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 118 |
| Part 2 - Treatment | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 12 |
| Part 2 - Treatment | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 28 |
| Part 2 - Treatment | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
Baseline characteristics
| Characteristic | Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Total | Part 1 and Part 2 Avapritinib (Formerly BLU-285) 300 mg or 400 mg QD | Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD | Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD | Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD | Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.7 years STANDARD_DEVIATION 12.21 | 59.4 years STANDARD_DEVIATION 10.97 | 59.4 years STANDARD_DEVIATION 11 | 48.3 years STANDARD_DEVIATION 20.82 | 61.7 years STANDARD_DEVIATION 8.31 | 61.5 years STANDARD_DEVIATION 10.05 | 60.2 years STANDARD_DEVIATION 11.84 | 60.2 years STANDARD_DEVIATION 6.77 |
| Body Mass Index (BMI) | 24.78 kg/m2 STANDARD_DEVIATION 4.22 | 26.09 kg/m2 STANDARD_DEVIATION 6.15 | 25.98 kg/m2 STANDARD_DEVIATION 6.22 | 27.15 kg/m2 STANDARD_DEVIATION 4.54 | 24.63 kg/m2 STANDARD_DEVIATION 5.16 | 23.78 kg/m2 STANDARD_DEVIATION 2.71 | 28.33 kg/m2 STANDARD_DEVIATION 3.76 | 31.61 kg/m2 STANDARD_DEVIATION 8.63 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 22 Participants | 22 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 12 Participants | 10 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 32 Participants | 28 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 181 Participants | 154 Participants | 3 Participants | 4 Participants | 5 Participants | 4 Participants | 6 Participants |
| Region of Enrollment Belgium | 0 participants | 16 participants | 13 participants | 0 participants | 1 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment France | 0 participants | 24 participants | 20 participants | 0 participants | 2 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Germany | 1 participants | 18 participants | 14 participants | 0 participants | 0 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Netherlands | 0 participants | 12 participants | 11 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment Poland | 0 participants | 8 participants | 8 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment South Korea | 0 participants | 17 participants | 17 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Spain | 0 participants | 11 participants | 11 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment United Kingdom | 1 participants | 28 participants | 23 participants | 1 participants | 0 participants | 0 participants | 3 participants | 0 participants |
| Region of Enrollment United States | 4 participants | 116 participants | 100 participants | 2 participants | 3 participants | 3 participants | 0 participants | 4 participants |
| Sex: Female, Male Female | 4 Participants | 96 Participants | 84 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 154 Participants | 133 Participants | 2 Participants | 3 Participants | 6 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 4 / 6 | 2 / 6 | 4 / 6 | 3 / 6 | 1 / 3 | 111 / 217 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 5 / 6 | 6 / 6 | 6 / 6 | 3 / 3 | 214 / 217 |
| serious Total, serious adverse events | 3 / 6 | 4 / 6 | 5 / 6 | 5 / 6 | 5 / 6 | 3 / 3 | 140 / 217 |
Outcome results
Primary
Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib
Patients with event(s) of dose-limiting toxicity
Time frame: Cycle 1 (28 days) of treatment
Population: Patients that completed Part 1 or had a DLT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib | 0 patients with event(s) of dose-limiting |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib | 0 patients with event(s) of dose-limiting |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib | 0 patients with event(s) of dose-limiting |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD | Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib | 0 patients with event(s) of dose-limiting |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD | Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib | 0 patients with event(s) of dose-limiting |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 300 mg QD | Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib | 0 patients with event(s) of dose-limiting |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 400 mg QD | Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib | 0 patients with event(s) of dose-limiting |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 600 mg QD | Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib | 2 patients with event(s) of dose-limiting |
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
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.
Population: 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 | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | Responder | 36 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | Non-Responder | 2 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | Responder | 10 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | Non-Responder | 40 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | Responder | 20 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | Non-Responder | 108 Participants |
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.
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
Population: Safety Population - all patients that received at least one dose of avapritinib
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with an Adverse Event | 6 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with a Serious Adverse Event | 3 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with an Adverse Event | 6 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with a Serious Adverse Event | 4 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with an Adverse Event | 6 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with a Serious Adverse Event | 5 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with an Adverse Event | 6 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 135 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with a Serious Adverse Event | 5 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with an Adverse Event | 6 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 200 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with a Serious Adverse Event | 5 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 300 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with an Adverse Event | 3 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 300 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with a Serious Adverse Event | 3 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 400 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with an Adverse Event | 216 participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 400 mg QD | Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE) | Participants with a Serious Adverse Event | 140 participants |
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
Time frame: Cycle 1 Day 15
Population: Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Apparent Oral Clearance at Steady State, Unadjusted for Bioavailability (CLss/F) | 21.8 L/h | Standard Deviation 12 |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Apparent Oral Clearance at Steady State, Unadjusted for Bioavailability (CLss/F) | 22.8 L/h | Standard Deviation 11.7 |
Secondary
Apparent Oral Clearance Unadjusted for Bioavailability (CL/F)
Apparent oral clearance unadjusted for bioavailability (CL/F) following a single dose of avapritinib
Time frame: Cycle 1 Day 1
Population: Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Apparent Oral Clearance Unadjusted for Bioavailability (CL/F) | 31.5 L/h | Standard Deviation 15.2 |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Apparent Oral Clearance Unadjusted for Bioavailability (CL/F) | 29.9 L/h | Standard Deviation 20.1 |
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
Time frame: Cycle 1 Day 1
Population: Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Apparent Volume of Distribution, Unadjusted for Bioavailability (Vz/F) | 1310 L | Standard Error 676 |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Apparent Volume of Distribution, Unadjusted for Bioavailability (Vz/F) | 1340 L | Standard Error 597 |
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
Time frame: Cycle 1 Day 1
Population: Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC 0-24) | 4510 h*ng/mL | Standard Deviation 1760 |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC 0-24) | 5310 h*ng/mL | Standard Deviation 2080 |
Secondary
Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady Sate (AUC0-τ,ss) (τ=24 h)
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
Population: Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady Sate (AUC0-τ,ss) (τ=24 h) | 16900 h*ng/mL | Standard Deviation 7230 |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady Sate (AUC0-τ,ss) (τ=24 h) | 21300 h*ng/mL | Standard Deviation 9250 |
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.
Time frame: Baseline and End of treatment
Population: Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Change From Baseline in Levels of KIT and PDGFRα Mutant Allele Fractions in Peripheral Blood | Change in PDGFRA MAF | 8.702 fraction of total |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Change From Baseline in Levels of KIT and PDGFRα Mutant Allele Fractions in Peripheral Blood | Change in KIT MAF | 14.398 fraction of total |
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.
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.
Population: patients with a starting dose of 300 or 400 mg QD
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | Clinical Benefit | 37 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | No Clinical Benefit | 1 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | Clinical Benefit | 26 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | No Clinical Benefit | 24 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | Clinical Benefit | 51 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | No Clinical Benefit | 77 Participants |
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
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.
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Duration of Response Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | 22.1 months |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Duration of Response Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | 19.2 months |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Duration of Response Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | 10.2 months |
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.
Time frame: Baseline and end of treatment
Population: Patients with pre-and post-treatment tumor biopsies. No patients provided a post-treatment biopsy.
Secondary
Maximum Plasma Drug Concentration (Cmax)
Maximum plasma drug concentration (Cmax) following a single dose of avapritinib
Time frame: Cycle 1 Day 1
Population: Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Maximum Plasma Drug Concentration (Cmax) | 305 ng/mL | Standard Deviation 153 |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Maximum Plasma Drug Concentration (Cmax) | 343 ng/mL | Standard Deviation 181 |
Secondary
Maximum Plasma Drug Concentration (Cmax) at Steady State
Maximum plasma drug concentration (Cmax) at steady state following 15 days of QD dosing
Time frame: Cycle 1 Day 15
Population: Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Maximum Plasma Drug Concentration (Cmax) at Steady State | 905 ng/mL | Standard Deviation 402 |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Maximum Plasma Drug Concentration (Cmax) at Steady State | 1140 ng/mL | Standard Deviation 469 |
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.
Time frame: Historical data collected at enrollment, all available data on prior therapy was collected
Population: Patients enrolled on any dose (Part 1 and Part 2) with data on progression-free survival for the most recent prior therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Median PFS on Last Prior Anti-cancer Therapy | 5.9 months |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Median PFS on Last Prior Anti-cancer Therapy | 31.0 months |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Median PFS on Last Prior Anti-cancer Therapy | 6.4 months |
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
Time frame: Cycle 1 Day 15
Population: Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at Steady State (C24,ss) | 593 ng/mL | Standard Deviation 263 |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at Steady State (C24,ss) | 760 ng/mL | Standard Deviation 343 |
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
Time frame: Cycle 1 Day 1
Population: Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose (C24) | 134 ng/mL | Standard Deviation 49.4 |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose (C24) | 185 ng/mL | Standard Deviation 80.2 |
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.
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.
Population: Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Progression-free Survival Per mRECIST Version 1.1 | 27.6 months |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Progression-free Survival Per mRECIST Version 1.1 | 5.5 months |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Progression-free Survival Per mRECIST Version 1.1 | 3.7 months |
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.
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.
Population: Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Response Rate Determined by Central Radiology Assessment Per Choi Criteria | Responder | 37 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Response Rate Determined by Central Radiology Assessment Per Choi Criteria | Non-responder | 1 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Response Rate Determined by Central Radiology Assessment Per Choi Criteria | Responder | 18 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Response Rate Determined by Central Radiology Assessment Per Choi Criteria | Non-responder | 32 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Response Rate Determined by Central Radiology Assessment Per Choi Criteria | Non-responder | 83 Participants |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 90 mg QD | Response Rate Determined by Central Radiology Assessment Per Choi Criteria | Responder | 45 Participants |
Secondary
Terminal Elimination Half-life (t1/2)
Terminal elimination half-life (t1/2) following a single dose of avapritinib
Time frame: Cycle 1 Day 1
Population: Patients enrolled in Part 1 or Part 2 with a starting dose of 300 or 400 mg QD and available PK samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Terminal Elimination Half-life (t1/2) | 32.1 h | Standard Deviation 15.6 |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Terminal Elimination Half-life (t1/2) | 43.5 h | Standard Deviation 28.4 |
Secondary
Time of Maximal Concentration (Tmax) at Steady State
Time of maximal concentration (Tmax) at steady state following 15 days of QD dosing
Time frame: Cycle 1 Day 15
Population: Patients enrolled in Part 1 and Part 2 with a starting dose of 300 or 400 mg QD and available samples for PK
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Time of Maximal Concentration (Tmax) at Steady State | 4.0 h |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Time of Maximal Concentration (Tmax) at Steady State | 3.99 h |
Secondary
Time to Maximum Plasma Drug Concentration (Tmax)
Cycle 1 Day 1 PK time to maximum plasma drug concentration (Tmax)
Time frame: Cycle 1 Day 1
Population: Patients enrolled in Part 1 and Part 2 with available samples for PK
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 30 mg QD | Time to Maximum Plasma Drug Concentration (Tmax) | 4.0 hours |
| Experimental: Part 1 Avapritinib (Formerly BLU-285) 60 mg QD | Time to Maximum Plasma Drug Concentration (Tmax) | 4.02 hours |