Advanced Systemic MastocytosisPhase 2NCT03580655
(PATHFINDER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis
A Phase 2 study testing Avapritinib in people with Advanced Systemic Mastocytosis and Aggressive Systemic Mastocytosis, run by Blueprint Medicines Corporation at 32 sites in 12 countries.
Trial summary
This is an open-label, single arm, Phase 2 study evaluating the efficacy and safety of avapritinib (BLU-285) in patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive SM (ASM), SM with associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Systemic Mastocytosis, Aggressive Systemic Mastocytosis, Systemic Mastocytosis With an Associated Hematologic Neoplasm
- What is being tested?
- Avapritinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 32 sitesin 12 countries
- Study dates
- 21 Nov 2018to 18 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have a diagnosis of aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) or mast cell leukemia (MCL) based on World Health Organization diagnostic criteria. Before enrollment, the Study Steering Committee must confirm the diagnosis of AdvSM (based on Central Pathology Laboratory assessment of bone marrow).
- Patient must have a serum tryptase ≥ 20 ng/mL.
- Patient must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 3.
Who cannot join
- Patient has received prior treatment with avapritinib.
- Patient has received any cytoreductive therapy (including midostaurin and other TKIs, hydroxyurea, azacitidine) or an investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon and any antibody therapy (eg, brentuximab vedotin) less than 28 days before obtaining screening BM biopsy for this study.
- Patient has eosinophilia and known positivity for the FIP1L1 PGDFRA fusion, unless the patient has demonstrated relapse or PD on prior imatinib therapy. Patients with eosinophilia (> 1.5 × 10^9/L), who do not have a detectable KIT D816 mutation, must be tested for a PDGFRA fusion mutation by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR).
- Patient has history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of study drug. The following are exempt from the 3-year limit: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
- Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480 msec.
- Patient has a known risk or recent history (12 months before the first dose of study drug) of intracranial bleeding (eg, brain aneurysm, concomitant vitamin K antagonist use).
Show all 12Show fewer
- Platelet count < 50,000/μL (within 4 weeks of the first dose of study drug) or receiving platelet transfusion(s).
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 x the upper limit of normal (ULN); no restriction if due to suspected liver infiltration by mast cells.
- Bilirubin >1.5 × ULN; no restriction if due to suspected liver infiltration by mast cells or Gilbert's disease. (In the case of Gilbert's disease, a direct bilirubin >2 × ULN would be an exclusion.)
- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 or creatinine > 1.5 × ULN.
- Patient has a primary brain malignancy or metastases to the brain.
- Patient has a history of a seizure disorder (eg, epilepsy) or requirement for antiseizure medication.
Trial locations and contacts
32 sites in 12 countries.
32 sites in 12 countries
United States12 sites
University of Michigan
Ann Arbor, Michigan, 48109
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
Rush University Medical Center
Chicago, Illinois, 60612
University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Mays Cancer Center
San Antonio, Texas, 78229
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford Cancer Institute
Stanford, California, 94305
The University of Kansas Cancer Center
Westwood, Kansas, 66205
Germany5 sites
Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltranslplantation
Aachen, 52074
Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie
Hamburg, 20246
Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, lnternistische Onkologie, Hämostaseologie
Leipzig, 04103
Universitätsmedizin Mannheim III. Medizinische Klinik
Mannheim, 68167
Klinik und Poliklinik für Innere Medizin III, Klinikum rechts der Isar der TU München
Munich, 81675
Italy3 sites
Azienda Ospedaliero-Universitaria Careggi, CRIMM - Centro di Ricerca ed Innovazione per le Malattie Mieloproliferative
Florence, 50134
A.O. OO.RR. S.Giovanni di Dio e Ruggi d'Aragona, University of Salerno
Salerno, 84131
Centro Ricerche Cliniche di Verona - Azienda Ospedaliera Universitaria Integrata di Verona
Verona, 37134
France2 sites
Hôpital Necker-Enfants Malades
Paris, 75015
CHU Toulouse - Hôpital Larrey
Toulouse, 31059
Poland2 sites
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
Gdansk, 80-214
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu, Klinice Hematologii, Nowotworów Krwi i Transplantacji Szpiku
Wroclaw, 50-367
United Kingdom2 sites
Beatson West of Scotland Cancer Centre - NHS Greater Glasgow and Clyde
Glasgow, G12 0YN
Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital
London, SE1 9RT
Austria1 site
Medizinische Universität Wien, Universitätsklinik für Innere Medizin I, Klinische Abteilung für Hämatologie und Hämostaseologie
Vienna, 1090
Denmark1 site
Odense University Hospital, Department of Haematology
Odense, DK-5000
Netherlands1 site
University Medical Center Groningen (UMCG)
Groningen, 9713 GZ
Spain1 site
lnstituto de Estudios de Mastocitosis de Castilla la Mancha, Hospital Virgen del Valle - Complejo Hospitalario de Toledo
Toledo, 45071
About this study
Official title: An Open-label, Single Arm, Phase 2 Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis
This is an open-label, single arm, Phase 2 study evaluating the efficacy and safety of avapritinib (BLU-285) in patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive SM (ASM), SM with associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL)
- Conditions
- Advanced Systemic Mastocytosis, Aggressive Systemic Mastocytosis, Systemic Mastocytosis With an Associated Hematologic Neoplasm, Mast Cell Leukemia
- Being tested
- Avapritinib
- Medical subject headings
- Mastocytosis, Systemic, Leukemia, Mast-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvapritinibDrug
Also called BLU-285
Avapritinib tablet
| Study group | Role | What they receive |
|---|---|---|
| Avapritinib | Experimental | Avapritinib will be administered as an immediate release tablet, orally, continuously, in 28-day cycles Receives: Drug: Avapritinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) Based on Modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (mIWG-MRT-ECNM) Response Criteria
ORR was defined as the percentage of participants with a confirmed best response of complete remission (CR), complete remission with partial recovery of peripheral blood counts (CRh), partial remission (PR), or clinical improvement (CI) by mIWG-MRT-ECNM criteria. The mIWG-MRT-ECNM criteria were based on findings from bone marrow biopsy and aspirate, and peripheral blood smear; bone marrow cytogenetics; other extracutaneous tissue biopsies (when available); liver and spleen imaging; and other clinical and laboratory parameters.
Measured: Baseline through Month 65
Secondary outcomes (21)
Mean Change From Baseline in Advanced Systemic Mastocytosis-Symptom Assessment Form (AdvSM-SAF) Total Symptom Score (TTS)
The AdvSM-SAF is a 10-item questionnaire that assesses eight symptoms specific to AdvSM. All eight symptoms are scored on a scale of 0 (absence of symptoms) to 10 (more severe symptoms) (up to 80 points maximum). Each symptom contributes to the TSS equally. The TSS was generated based on average scores for each 7-day period. An increase in score from 0 (no symptoms) to 80 (worst symptoms represents a worse symptoms outcome. Participants completed the AdvSM-SAF daily using an electronic diary (eDiary). Each cycle is 28 days long.
Measured: Baseline up to Month 6 (Cycle 6, Day 1)
ORR Based on mIWG-MRT-ECNM Response Criteria as Assessed by Local Investigator
ORR was defined as the percentage of participants with a confirmed best response of CR, CRh, PR, or CI by mIWG-MRT-ECNM criteria. The mIWG-MRT-ECNM criteria were based on findings from bone marrow biopsy and aspirate, and peripheral blood smear; bone marrow cytogenetics; other extracutaneous tissue biopsies (when available); liver and spleen imaging; and other clinical and laboratory parameters.
Measured: Baseline through Month 19
Time-to-Response (TTR)
TTR was defined as the time from first dose to the time of initial evaluation of clinical improvement (CI) or better. Here, 'Overall Number of Participants Analyzed' signifies those participants with a confirmed best response of CR, CRh, PR, and CI by mIWG-MRT-ECNM criteria.
Measured: Baseline through Month 65
Duration of Response (DOR)
DOR was defined as the time from initial documentation of a CI or better to the time of initial documentation of confirmed progressive disease (PD) or death due to any cause, whichever occurred first. For responders who had not progressed or died at the time of analysis, DOR was censored at the last response assessment that was stable disease (SD) or better. Here, 'Overall Number of Participants Analyzed' signifies those participants with a confirmed best response of CR, CRh, PR, and CI by mIWG-MRT-ECNM criteria.
Measured: Baseline through Month 65
Progression-free Survival (PFS)
PFS was defined as time from first dose to the time of initial documentation of confirmed PD or death due to any cause, whichever occurred first. Participants who had not progressed or died at the time of analysis were censored at the last response assessment that was SD or better.
Measured: Baseline through Month 65
Overall Survival (OS)
OS was defined as time from first dose to the time of death due to any cause. Participants who were known to be alive or are lost to follow-up were censored at the last time point they were known to be alive.
Measured: Baseline through Month 65
Objective Response Rate
The objective response rate was defined as the number of participants with a confirmed best response of morphologic complete remission, morphologic complete remission with partial recovery of peripheral blood counts, or morphologic partial remission by pure pathologic response (PPR) criteria. The PPR criteria are a modification of the mIWG-MRT-ECNM criteria that define deep responses where direct measure of the disease burden determined the response and focus on objective changes (bone marrow mast cell burden, serum tryptase, and complete blood count).
Measured: Baseline through Month 65
Clinical Benefit Rate
The clinical benefit rate was defined as the percentage of participants with a confirmed best response of CR, CRh, PR, CI, and SD by mIWG-MRT-ECNM criteria.
Measured: Baseline through Month 65
Percent Change From Baseline in Bone Marrow Mast Cells
Bone marrow biopsies and aspirates and peripheral blood smears were obtained for systemic mastocytosis response assessment according to mIWG-MRT-ECNM criteria. Each cycle is 28 days long.
Measured: Baseline up to Month 65
Percent Change From Baseline in Serum Tryptase
Blood samples were collected to characterize the change in serum tryptase concentration during treatment with avapritinib. Each cycle is 28 days long.
Measured: Baseline up to Month 65
Percent Change From Baseline in V-kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog Aspartate 816 Valine (KIT D816V) Mutation Burden
Bone marrow aspirate and PB samples were collected to characterize the KIT D816V mutation allele fraction. Each cycle is 28 days long.
Measured: Baseline up to Month 65
Percent Change From Baseline in Liver Volume by Imaging
Assessment of liver volume was performed using serial imaging with magnetic resonance imaging (MRI). Response was defined as resolution of palpable hepatomegaly (CR). Each cycle is 28 days long.
Measured: Baseline up to Month 65
Percent Change From Baseline in Spleen Volume by Imaging
Assessment of spleen volume was performed using serial imaging with MRI. Response was defined as ≥35% reduction in spleen volume (PR) or resolution of palpable splenomegaly (CR). Each cycle is 28 days long.
Measured: Baseline up to Month 65
Mean Change From Baseline in AdvSM-SAF Skin and Gastrointestinal Domain Scores at Month 10
The AdvSM-SAF is a 10-item questionnaire that assesses symptoms and functional domains specific to AdvSM. Eight symptoms are scored on a scale of 0 to 10 for severity and 2 symptoms (vomiting and diarrhea) are scored for number of episodes. The skin domain is scored on a scale of 0-30, where 0 represents an absence of symptoms and 30 the most severe symptom experience. Similarly, the gastrointestinal domain is scored on a scale of 0-40, where 0 represents an absence of symptoms and 40 the most severe symptom experience. Skin and gastrointestinal domain scores were generated based on average scores for each 7-day period. An increase in score represents a worse symptoms outcome. Participants completed the AdvSM-SAF daily using an eDiary.
Measured: Baseline, Month 10
Mean Change From Baseline in AdvSM-SAF Individual Symptom Scores (Severity) at Month 10
The AdvSM-SAF is a 10-item questionnaire that assesses symptoms and functional domains specific to AdvSM. Individual symptom scores are generated based on average scores for each 7-day period. Eight symptoms are scored on a scale of 0 to 10 for severity. An increase in score represents a worse symptoms outcome. Participants completed the AdvSM-SAF daily using an eDiary.
Measured: Baseline, Month 10
Mean Change From Baseline in AdvSM-SAF Individual Symptom Scores (Episodes) at Month 10
The AdvSM-SAF is a 10-item questionnaire that assesses symptoms and functional domains specific to AdvSM. Individual symptom scores are generated based on average scores for each 7-day period. Two symptoms (vomiting and diarrhea) are scored for number of episodes. An increase in score represents a worse symptoms outcome. Participants completed the AdvSM-SAF daily using an eDiary.
Measured: Baseline, Month 10
Change From Baseline in Patient's Global Impression of Symptom Severity (PGIS)
The PGIS is a single-item scale that assesses a participant's perception of disease symptoms at a point in time. Scores range from 0 to 4 points, with higher values representing worse symptom outcomes. It is widely used to evaluate a participant's overall sense of whether a treatment has been beneficial. Each cycle is 28 days long.
Measured: Baseline, Cycle 1, Day 15 and Day 1 of Cycle 2, Cycle 3, Cycle 5, Cycle 7, Cycle 9, Cycle 11, Cycle 14, and Cycle 17 (28 days/cycle)
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Quality of life was assessed using EORTC QLQ-C30, which is a 30-item questionnaire that includes 5 functional domains (physical, cognitive, role, emotional, and social) and a global health status scale. Twenty-eight questions are scored from 1 (not at all) to 4 (very much), while the other 2 are scored from 1 (very poor) to 7 (excellent). The calculated average is standardized using a linear transformation to a standardized scale of 0 to 100, with a decrease in score representing a decrease in quality of life. Each cycle is 28 days long.
Measured: Baseline, Cycle 1, Day 15 and Day 1 of Cycle 2, Cycle 3, Cycle 5, Cycle 7, Cycle 9, Cycle 11, Cycle 14, and Cycle 17 (28 days/cycle)
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE)
A TEAE was defined as any adverse events that occurred between the first dose of a study drug through 30 days after the last dose of any study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Measured: Baseline through Month 65
Maximum Plasma Concentration (Cmax) of a Single Dose of Avapritinib
Blood samples were collected at specified timepoints. Results reported as nanograms/milliliter (ng/mL).
Measured: Day 1 of Cycle 1 (1 hour postdose) (28 days/cycle)
Correlation Between TSS and Serum Tryptase
The change in baseline for AdvSM-SAF TSS was correlated with the change in baseline for serum tryptase. Spearman correlation coefficients were performed with corresponding scatter plots on change from baseline.
Measured: Baseline, Month 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2018
- Study start21 Nov 2018
- Primary completion18 Dec 2024
- Study completion18 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Advanced Systemic MastocytosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Blueprint Medicines Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03580655
- Sponsor's protocol ID
- BLU-285-2202
- Other IDs
- 2017-004836-13, 2017
- Status last verified
- Sep 2026
- First submitted
- 3 May 2018
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Gotlib J, Reiter A, Radia DH, Alvarez-Twose I, Deininger MW, George TI, Panse J, Mital A, Pettit KM, Vannucchi AM, Platzbecker U, Hermine O, Elshoury A, Livideanu CB, Mesa R, Ustun C, Triggiani M, Dybedal I, Jurcic JG, Zanotti R, Oh ST, Yacoub A, Hexner EO, Bose P, Lee SG, Sperr WR, Griffiths EA, Butler M, Lubke J, Bidollari I, Lin HM, Rylova S, Dimitrijevic S, Munoz-Gonzalez JI, DeAngelo DJ. Efficacy and safety of avapritinib in advanced systemic mastocytosis: 4-year follow-up of the PATHFINDER study. Blood Adv. 2026 May 26;10(10):3676-3689. doi: 10.1182/bloodadvances.2025017519.
PubMed 41604606Reiter A, Gotlib J, Alvarez-Twose I, Radia DH, Lubke J, Bobbili PJ, Wang A, Norregaard C, Dimitrijevic S, Sullivan E, Louie-Gao M, Schwaab J, Galinsky IA, Perkins C, Sperr WR, Sriskandarajah P, Chin A, Sendhil SR, Duh MS, Valent P, DeAngelo DJ. Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis. Leukemia. 2022 Aug;36(8):2108-2120. doi: 10.1038/s41375-022-01615-z. Epub 2022 Jul 5.
PubMed 35790816Reiter A, Schwaab J, DeAngelo DJ, Gotlib J, Deininger MW, Pettit KM, Alvarez-Twose I, Vannucchi AM, Panse J, Platzbecker U, Hermine O, Dybedal I, Lin HM, Rylova SN, Ehlert K, Dimitrijevic S, Radia DH. Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis. Blood Adv. 2022 Nov 8;6(21):5750-5762. doi: 10.1182/bloodadvances.2022007539.
PubMed 35640224Gotlib J, Reiter A, Radia DH, Deininger MW, George TI, Panse J, Vannucchi AM, Platzbecker U, Alvarez-Twose I, Mital A, Hermine O, Dybedal I, Hexner EO, Hicks LK, Span L, Mesa R, Bose P, Pettit KM, Heaney ML, Oh ST, Sen J, Lin HM, Mar BG, DeAngelo DJ. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. Nat Med. 2021 Dec;27(12):2192-2199. doi: 10.1038/s41591-021-01539-8. Epub 2021 Dec 6.
PubMed 34873345
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single Arm, Phase 2 Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis
- ClinicalTrials.gov ID
- NCT03580655
- Acronym / sponsor ID
- BLU-285-2202
- Conditions
- Advanced Systemic Mastocytosis, Aggressive Systemic Mastocytosis, Systemic Mastocytosis With an Associated Hematologic Neoplasm, Mast Cell Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Blueprint Medicines CorporationIndustry (pharma, biotech, devices)
- Study start
- 21 Nov 2018 (actual)
- Primary completion
- 18 Dec 2024 (actual)
- Study completion
- 18 Dec 2024 (actual)
- First posted
- 9 Jul 2018 (actual)
- Results
- Posted 24 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, single arm, Phase 2 study evaluating the efficacy and safety of avapritinib (BLU-285) in patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive SM (ASM), SM with associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Avapritinib | Experimental | Drug: AvapritinibAvapritinib will be administered as an immediate release tablet, orally, continuously, in 28-day cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patient must have a diagnosis of aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) or mast cell leukemia (MCL) based on World Health Organization diagnostic criteria. Before enrollment, the Study Steering Committee must confirm the diagnosis of AdvSM (based on Central Pathology Laboratory assessment of bone marrow).
- Patient must have a serum tryptase ≥ 20 ng/mL.
- Patient must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 3.
Key exclusion criteria (12 listed)
- Patient has received prior treatment with avapritinib.
- Patient has received any cytoreductive therapy (including midostaurin and other TKIs, hydroxyurea, azacitidine) or an investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon and any antibody therapy (eg, brentuximab vedotin) less than 28 days before obtaining screening BM biopsy for this study.
- Patient has eosinophilia and known positivity for the FIP1L1 PGDFRA fusion, unless the patient has demonstrated relapse or PD on prior imatinib therapy. Patients with eosinophilia (> 1.5 × 10^9/L), who do not have a detectable KIT D816 mutation, must be tested for a PDGFRA fusion mutation by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR).
- Patient has history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of study drug. The following are exempt from the 3-year limit: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
- Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480 msec.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvapritinibAlso: BLU-285Avapritinib tablet | Drug | Avapritinib |
Primary outcome
Overall Response Rate (ORR) Based on Modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (mIWG-MRT-ECNM) Response Criteria
Time frame: Baseline through Month 65
ORR was defined as the percentage of participants with a confirmed best response of complete remission (CR), complete remission with partial recovery of peripheral blood counts (CRh), partial remission (PR), or clinical improvement (CI) by mIWG-MRT-ECNM criteria. The mIWG-MRT-ECNM criteria were based on findings from bone marrow biopsy and aspirate, and peripheral blood smear; bone marrow cytogenetics; other extracutaneous tissue biopsies (when available); liver and spleen imaging; and other clinical and laboratory parameters.
21 secondary outcomes
Mean Change From Baseline in Advanced Systemic Mastocytosis-Symptom Assessment Form (AdvSM-SAF) Total Symptom Score (TTS)
Time frame: Baseline up to Month 6 (Cycle 6, Day 1)
ORR Based on mIWG-MRT-ECNM Response Criteria as Assessed by Local Investigator
Time frame: Baseline through Month 19
Time-to-Response (TTR)
Time frame: Baseline through Month 65
Duration of Response (DOR)
Time frame: Baseline through Month 65
Progression-free Survival (PFS)
Time frame: Baseline through Month 65
Overall Survival (OS)
Time frame: Baseline through Month 65
Objective Response Rate
Time frame: Baseline through Month 65
Clinical Benefit Rate
Time frame: Baseline through Month 65
Percent Change From Baseline in Bone Marrow Mast Cells
Time frame: Baseline up to Month 65
Percent Change From Baseline in Serum Tryptase
Time frame: Baseline up to Month 65
Percent Change From Baseline in V-kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog Aspartate 816 Valine (KIT D816V) Mutation Burden
Time frame: Baseline up to Month 65
Percent Change From Baseline in Liver Volume by Imaging
Time frame: Baseline up to Month 65
Percent Change From Baseline in Spleen Volume by Imaging
Time frame: Baseline up to Month 65
Mean Change From Baseline in AdvSM-SAF Skin and Gastrointestinal Domain Scores at Month 10
Time frame: Baseline, Month 10
Mean Change From Baseline in AdvSM-SAF Individual Symptom Scores (Severity) at Month 10
Time frame: Baseline, Month 10
Mean Change From Baseline in AdvSM-SAF Individual Symptom Scores (Episodes) at Month 10
Time frame: Baseline, Month 10
Change From Baseline in Patient's Global Impression of Symptom Severity (PGIS)
Time frame: Baseline, Cycle 1, Day 15 and Day 1 of Cycle 2, Cycle 3, Cycle 5, Cycle 7, Cycle 9, Cycle 11, Cycle 14, and Cycle 17 (28 days/cycle)
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Time frame: Baseline, Cycle 1, Day 15 and Day 1 of Cycle 2, Cycle 3, Cycle 5, Cycle 7, Cycle 9, Cycle 11, Cycle 14, and Cycle 17 (28 days/cycle)
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE)
Time frame: Baseline through Month 65
Maximum Plasma Concentration (Cmax) of a Single Dose of Avapritinib
Time frame: Day 1 of Cycle 1 (1 hour postdose) (28 days/cycle)
Correlation Between TSS and Serum Tryptase
Time frame: Baseline, Month 10
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41604606Gotlib J, Reiter A, Radia DH, Alvarez-Twose I, Deininger MW, George TI, Panse J, Mital A, Pettit KM, Vannucchi AM, Platzbecker U, Hermine O, Elshoury A, Livideanu CB, Mesa R, Ustun C, Triggiani M, Dybedal I, Jurcic JG, Zanotti R, Oh ST, Yacoub A, Hexner EO, Bose P, Lee SG, Sperr WR, Griffiths EA, Butler M, Lubke J, Bidollari I, Lin HM, Rylova S, Dimitrijevic S, Munoz-Gonzalez JI, DeAngelo DJ. Efficacy and safety of avapritinib in advanced systemic mastocytosis: 4-year follow-up of the PATHFINDER study. Blood Adv. 2026 May 26;10(10):3676-3689. doi: 10.1182/bloodadvances.2025017519.
- Derived from this study: PubMed 35790816Reiter A, Gotlib J, Alvarez-Twose I, Radia DH, Lubke J, Bobbili PJ, Wang A, Norregaard C, Dimitrijevic S, Sullivan E, Louie-Gao M, Schwaab J, Galinsky IA, Perkins C, Sperr WR, Sriskandarajah P, Chin A, Sendhil SR, Duh MS, Valent P, DeAngelo DJ. Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis. Leukemia. 2022 Aug;36(8):2108-2120. doi: 10.1038/s41375-022-01615-z. Epub 2022 Jul 5.
- Derived from this study: PubMed 35640224Reiter A, Schwaab J, DeAngelo DJ, Gotlib J, Deininger MW, Pettit KM, Alvarez-Twose I, Vannucchi AM, Panse J, Platzbecker U, Hermine O, Dybedal I, Lin HM, Rylova SN, Ehlert K, Dimitrijevic S, Radia DH. Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis. Blood Adv. 2022 Nov 8;6(21):5750-5762. doi: 10.1182/bloodadvances.2022007539.
- Derived from this study: PubMed 34873345Gotlib J, Reiter A, Radia DH, Deininger MW, George TI, Panse J, Vannucchi AM, Platzbecker U, Alvarez-Twose I, Mital A, Hermine O, Dybedal I, Hexner EO, Hicks LK, Span L, Mesa R, Bose P, Pettit KM, Heaney ML, Oh ST, Sen J, Lin HM, Mar BG, DeAngelo DJ. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. Nat Med. 2021 Dec;27(12):2192-2199. doi: 10.1038/s41591-021-01539-8. Epub 2021 Dec 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
32 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avapritinib in people with Advanced Systemic Mastocytosis and Aggressive Systemic Mastocytosis, run by Blueprint Medicines Corporation at 32 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Germany, Italy, France, Poland and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) Based on Modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (mIWG-MRT-ECNM) Response Criteria (time frame: Baseline through Month 65). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03580655, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.