TriangleNCT02508532 · CITED IN SOURCE DOCUMENTS
(NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE1
- Status at capture
- COMPLETED
- Registry last update
- 2022-06-21
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).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib
Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE)
Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1
Maximum Plasma Drug Concentration (Cmax)
Time to Maximum Plasma Drug Concentration (Tmax)
Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose (C24)
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC 0-24)
Apparent Oral Clearance Unadjusted for Bioavailability (CL/F)
Apparent Volume of Distribution, Unadjusted for Bioavailability (Vz/F)
Terminal Elimination Half-life (t1/2)
Maximum Plasma Drug Concentration (Cmax) at Steady State
Time of Maximal Concentration (Tmax) at Steady State
Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at Steady State (C24,ss)
Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady Sate (AUC0-τ,ss) (τ=24 h)
Progression-free Survival Per mRECIST Version 1.1
Apparent Oral Clearance at Steady State, Unadjusted for Bioavailability (CLss/F)
Clinical Benefit Rate Determined by Central Radiology Assessment Per mRECIST, Version 1.1
Response Rate Determined by Central Radiology Assessment Per Choi Criteria
Duration of Response Determined by Central Radiology Assessment Per mRECIST, Version 1.1
Median PFS on Last Prior Anti-cancer Therapy
Change From Baseline in Levels of KIT and PDGFRα Mutant Allele Fractions in Peripheral Blood
KIT, PDGFRA, and Other Cancer-relevant Mutations Present in Tumor Tissue at Baseline and EOT
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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 * Group 3: Patients known to be KIT wild type.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Part 1: Patients received a starting dose of 30 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued. Patients received avapritinib in continuous 28 day cycles until discontinuation.
- intervention Names
- Drug: Avapritinib
- label
- Part 1 Avapritinib (formerly BLU-285) 30 mg QD
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Avapritinib
- label
- Part 1 Avapritinib (formerly BLU-285) 60 mg QD
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Avapritinib
- label
- Part 1 Avapritinib (formerly BLU-285) 90 mg QD
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Avapritinib
- label
- Part 1 Avapritinib (formerly BLU-285) 135 mg QD
- type
- EXPERIMENTAL
- description
- 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. .
- intervention Names
- Drug: Avapritinib
- label
- Part 1 Avapritinib (formerly BLU-285) 200 mg QD
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Avapritinib
- label
- Part 1 Avapritinib (formerly BLU-285) 300 mg QD
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Avapritinib
- label
- Part 1 Avapritinib (formerly BLU-285) 400 mg QD
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Avapritinib
- label
- Part 1 Avapritinib (formerly BLU-285) 600 mg QD
- type
- EXPERIMENTAL
- description
- Part 1 and Part 2: Patients enrolled in Part 1 and Part 2 at a starting dose of 300 or 400 mg QD were included in the Part1/Part 2 safety and efficacy analysis. Patients received avapritinib in continuous 28 day cycles until discontinuation.
- intervention Names
- Drug: Avapritinib
- label
- Part 1 and Part 2 Avapritinib (formerly BLU-285) 300 mg or 400 mg QD
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- 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
- 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
- description
- avapritinib tablets
- name
- Avapritinib
- other Names
- BLU-285
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- SEQUENTIAL
- intervention Model Description
- Dose Escalation and Dose Expansion
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 250
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Patients with event(s) of dose-limiting toxicity
- measure
- Part 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Avapritinib
- time Frame
- Cycle 1 (28 days) of treatment
- description
- The overall safety profile of the drug was assessed by reviewing the number of patients with AEs, SAEs and other events. There was no formal statistical analysis. Safety assessments continued for the duration of treatment.
- measure
- Parts 1 and 2: Number of Patients With Adverse Events (AE) and Serious Adverse Events (SAE)
- 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
- description
- To evaluate objective response rate (ORR) determined by central radiology assessment per mRECIST, version 1.1 in patients with advanced GIST treated with avapritinib. A complete response per modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) is defined as complete disappearance of all target lesions. A partial response is defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Overall Response (OR) = CR + PR
- measure
- Part 2: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1
- 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.
- secondary Outcomes
- description
- Maximum plasma drug concentration (Cmax) following a single dose of avapritinib
- measure
- Maximum Plasma Drug Concentration (Cmax)
- time Frame
- Cycle 1 Day 1
- description
- Cycle 1 Day 1 PK time to maximum plasma drug concentration (Tmax)
- measure
- Time to Maximum Plasma Drug Concentration (Tmax)
- time Frame
- Cycle 1 Day 1
- description
- Plasma drug concentration at 24 hours postdose prior to the next daily dose (C24) following a single dose of avapritinib
- measure
- Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose (C24)
- time Frame
- Cycle 1 Day 1
- description
- Area under the plasma concentration-time curve from time 0 to 24 hours (AUC 0-24) following a single dose of avapritinib
- measure
- Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC 0-24)
- time Frame
- Cycle 1 Day 1
- description
- Apparent oral clearance unadjusted for bioavailability (CL/F) following a single dose of avapritinib
- measure
- Apparent Oral Clearance Unadjusted for Bioavailability (CL/F)
- time Frame
- Cycle 1 Day 1
- description
- Apparent volume of distribution, unadjusted for bioavailability (Vz/F) following a single dose of avapritinib
- measure
- Apparent Volume of Distribution, Unadjusted for Bioavailability (Vz/F)
- time Frame
- Cycle 1 Day 1
- description
- Terminal elimination half-life (t1/2) following a single dose of avapritinib
- measure
- Terminal Elimination Half-life (t1/2)
- time Frame
- Cycle 1 Day 1
- description
- Maximum plasma drug concentration (Cmax) at steady state following 15 days of QD dosing
- measure
- Maximum Plasma Drug Concentration (Cmax) at Steady State
- time Frame
- Cycle 1 Day 15
- description
- Time of maximal concentration (Tmax) at steady state following 15 days of QD dosing
- measure
- Time of Maximal Concentration (Tmax) at Steady State
- time Frame
- Cycle 1 Day 15
- description
- Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at steady state (C24,ss) following 15 days of QD dosing
- measure
- Plasma Drug Concentration at 24 Hours Postdose Prior to the Next Daily Dose at Steady State (C24,ss)
- time Frame
- Cycle 1 Day 15
- description
- Area under the plasma concentration-time curve over the dosing interval at steady sate (AUC0-τ,ss) (τ=24 h) following 15 days of QD dosing
- measure
- Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady Sate (AUC0-τ,ss) (τ=24 h)
- time Frame
- Cycle 1 Day 15
- description
- Progression-free survival is defined as the time in months from the start of treatment to the date of first documented progression or death due to any cause. Progression-free survival determined by central radiological assessment per modified Response Evaluation Criteria in Solid Tumors (mRECIST), version 1.1 in patients with advanced GIST. A progressively growing tumor must meet the following criteria: a) the target lesions must be greater or equal to 2cm in size and be a new GIST active lesion or b) the target lesions must be expanding on at least 2 sequential imaging studies.
- measure
- Progression-free Survival Per mRECIST Version 1.1
- 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.
Full study description
- 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).
Source references
- references
- citation
- 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.
- pmid
- 34343033
- type
- DERIVED
- citation
- 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.
- pmid
- 33740926
- type
- DERIVED
- citation
- 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.
- pmid
- 33465704
- type
- DERIVED
- citation
- Joseph CP, Abaricia SN, Angelis MA, Polson K, Jones RL, Kang YK, Riedel RF, Schoffski P, Serrano C, Trent J, Tetzlaff ED, Si TD, Zhou T, Doyle A, Bauer S, Roche M, Havnaer T. Optimal Avapritinib Treatment Strategies for Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors. Oncologist. 2021 Apr;26(4):e622-e631. doi: 10.1002/onco.13632. Epub 2021 Jan 5.
- pmid
- 33301227
- type
- DERIVED
- citation
- 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.
- pmid
- 32615108
- type
- DERIVED
- citation
- 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.
- pmid
- 30274985
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-5f2e310fdbe10917f039
- requested nct id
- NCT02508532
- primary nct id
- NCT02508532
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source file sha256
- dc65ea27069b2a555937675046eef3875af3e654cbd5b12dc4e6759d872d85c7
- payload sha256
- 090c700034c8e9f3345e69c3e3fbff3b740fb1c46922c1ae750d62b8fb566d40
- payload
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-5f2e310fdbe10917f039
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT02508532
- occurrences
- context exact
- nib in patients with a <em class="gene-name">PDGFRA</em> D842V variant):</p> <div class="pdq-content-list"><ol id="_419"><li><a href="/clinicaltrials/NCT02508532">NAVIGATOR</a> (NCT02508532) was a phase I, single-arm, open-label trial of 56 patients with a <em class="gene-name">PDGFRA</em> D842V variant. Patients receiv
- end
- 138678
- exact text
- NCT02508532
- start
- 138667
- context exact
- lass="gene-name">PDGFRA</em> D842V variant):</p> <div class="pdq-content-list"><ol id="_419"><li><a href="/clinicaltrials/NCT02508532">NAVIGATOR</a> (NCT02508532) was a phase I, single-arm, open-label trial of 56 patients with a <em class="gene-name">PDGFRA</em> D842V variant. Patients received avapritinib at a daily do
- end
- 138706
- exact text
- NCT02508532
- start
- 138695
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/nci/raw/56f3a793bc98f402b9.html
- source file sha256
- dc65ea27069b2a555937675046eef3875af3e654cbd5b12dc4e6759d872d85c7
- source json pointer
- Source null
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source retrieved at
- 2026-09-09T23:22:19.967119+00:00
- source string basis
- UTF-8_text_with_universal_newline_translation
- source string sha256
- ad589beab368bd0fb781a6e8f9ce2015eb8c80c2e12bd848c86e9cc1d3cce153
- source title
- Gastrointestinal Stromal Tumors Treatment (PDQ®)–Health Professional Version
- source update dates
- context
- Updated: December 13, 2024
- datetime
- 2024-12-13T12:00:00Z
- display
- December 13, 2024
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-e811f5edbd79c7f343f5
- requested nct id
- NCT02508532
- primary nct id
- NCT02508532
- source kind
- fda_spl_label
- source record id
- beacc534-14e1-4fd2-978f-5646edd537f0
- source file sha256
- a9df7a5786dc51557d38f2a0881b5b5e9ae02ae396a6798e39ac96f586bcc5e6
- payload sha256
- eda6bb0aac0dddba43b26f6039b9b4656159fa0e7072561792b8e0010d596fd3
- payload
- application numbers
- NDA212608
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-e811f5edbd79c7f343f5
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT02508532
- occurrences
- context exact
- 14 CLINICAL STUDIES 14.1 Gastrointestinal Stromal Tumors The efficacy of AYVAKIT was demonstrated in NAVIGATOR (NCT02508532), a multi-center, single-arm, open-label clinical trial. Eligible patients were required to have a confirmed diagnosis of GIST and an ECOG performance status (
- end
- 123
- exact text
- NCT02508532
- start
- 112
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00600.json
- source file sha256
- a9df7a5786dc51557d38f2a0881b5b5e9ae02ae396a6798e39ac96f586bcc5e6
- source json pointer
- /results/40/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- beacc534-14e1-4fd2-978f-5646edd537f0
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- ace6d9bb70d9cdd769257a9e26931b79d9233fdd2be2d01b8f2cb7491c309f26
- spl effective time
- 20260805
- spl set id
- 645c887c-8cd4-4623-8da9-ac223d71a8b9
Preserved source evidence · Not medical advice