(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

April 22, 2026 updated by: Blueprint Medicines Corporation

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

107

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Medizinische Universität Wien, Universitätsklinik für Innere Medizin I, Klinische Abteilung für Hämatologie und Hämostaseologie
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5B 1W8
        • St. Michael's Hospital
  • Denmark
      • Odense, Denmark, DK-5000
        • Odense University Hospital, Department of Haematology
  • France
      • Paris, France, 75015
        • Hopital Necker-Enfants Malades
      • Toulouse, France, 31059
        • CHU Toulouse - Hopital Larrey
  • Germany
      • Aachen, Germany, 52074
        • Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltranslplantation
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie
      • Leipzig, Germany, 04103
        • Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, lnternistische Onkologie, Hämostaseologie
      • Mannheim, Germany, 68167
        • Universitätsmedizin Mannheim III. Medizinische Klinik
      • Munich, Germany, 81675
        • Klinik und Poliklinik für Innere Medizin III, Klinikum rechts der Isar der TU München
  • Italy
      • Florence, Italy, 50134
        • Azienda Ospedaliero-Universitaria Careggi, CRIMM - Centro di Ricerca ed Innovazione per le Malattie Mieloproliferative
      • Salerno, Italy, 84131
        • A.O. OO.RR. S.Giovanni di Dio e Ruggi d'Aragona, University of Salerno
      • Verona, Italy, 37134
        • Centro Ricerche Cliniche di Verona - Azienda Ospedaliera Universitaria Integrata di Verona
  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen (UMCG)
  • Norway
      • Oslo, Norway, 0372
        • Oslo University Hospital-Rikshospitalet, Hematology
  • Poland
      • Gdansk, Poland, 80-214
        • Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
      • Wroclaw, Poland, 50-367
        • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu, Klinice Hematologii, Nowotworów Krwi i Transplantacji Szpiku
  • Spain
      • Toledo, Spain, 45071
        • lnstituto de Estudios de Mastocitosis de Castilla la Mancha, Hospital Virgen del Valle - Complejo Hospitalario de Toledo
  • United Kingdom
      • Glasgow, United Kingdom, G12 0YN
        • Beatson West of Scotland Cancer Centre - NHS Greater Glasgow and Clyde
      • London, United Kingdom, SE1 9RT
        • Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital
  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Kansas
      • Westwood, Kansas, United States, 66205
        • The University of Kansas Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Comprehensive Cancer Center
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania, Abramson Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas, MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • Mays Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. 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).
  2. Patient must have a serum tryptase ≥ 20 ng/mL.
  3. Patient must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 3.

Key Exclusion Criteria:

  1. Patient has received prior treatment with avapritinib.
  2. 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.
  3. 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).
  4. 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.
  5. Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480 msec.
  6. 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).
  7. Platelet count < 50,000/μL (within 4 weeks of the first dose of study drug) or receiving platelet transfusion(s).
  8. 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.
  9. 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.)
  10. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 or creatinine > 1.5 × ULN.
  11. Patient has a primary brain malignancy or metastases to the brain.
  12. Patient has a history of a seizure disorder (eg, epilepsy) or requirement for antiseizure medication.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Avapritinib
Avapritinib will be administered as an immediate release tablet, orally, continuously, in 28-day cycles
Drug: Avapritinib
Avapritinib tablet
Other Names:
  • BLU-285

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline through Month 65

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
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
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.
Baseline through Month 19
Time-to-Response (TTR)
Time Frame: Baseline through Month 65
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.
Baseline through Month 65
Duration of Response (DOR)
Time Frame: Baseline through Month 65
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.
Baseline through Month 65
Progression-free Survival (PFS)
Time Frame: Baseline through Month 65
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.
Baseline through Month 65
Overall Survival (OS)
Time Frame: Baseline through Month 65
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.
Baseline through Month 65
Objective Response Rate
Time Frame: Baseline through Month 65
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).
Baseline through Month 65
Clinical Benefit Rate
Time Frame: Baseline through Month 65
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.
Baseline through Month 65
Percent Change From Baseline in Bone Marrow Mast Cells
Time Frame: Baseline up to Month 65
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.
Baseline up to Month 65
Percent Change From Baseline in Serum Tryptase
Time Frame: Baseline up to Month 65
Blood samples were collected to characterize the change in serum tryptase concentration during treatment with avapritinib. Each cycle is 28 days long.
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
Bone marrow aspirate and PB samples were collected to characterize the KIT D816V mutation allele fraction. Each cycle is 28 days long.
Baseline up to Month 65
Percent Change From Baseline in Liver Volume by Imaging
Time Frame: Baseline up to Month 65
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.
Baseline up to Month 65
Percent Change From Baseline in Spleen Volume by Imaging
Time Frame: Baseline up to Month 65
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.
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
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.
Baseline, Month 10
Mean Change From Baseline in AdvSM-SAF Individual Symptom Scores (Severity) at Month 10
Time Frame: Baseline, 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.
Baseline, Month 10
Mean Change From Baseline in AdvSM-SAF Individual Symptom Scores (Episodes) at Month 10
Time Frame: Baseline, 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.
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)
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.
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)
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.
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
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.
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)
Blood samples were collected at specified timepoints. Results reported as nanograms/milliliter (ng/mL).
Day 1 of Cycle 1 (1 hour postdose) (28 days/cycle)
Correlation Between TSS and Serum Tryptase
Time Frame: Baseline, Month 10
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.
Baseline, Month 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Blueprint Medicines Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 21, 2018

Primary Completion (Actual)

December 18, 2024

Study Completion (Actual)

December 18, 2024

Study Registration Dates

First Submitted

May 3, 2018

First Submitted That Met QC Criteria

June 26, 2018

First Posted (Actual)

July 9, 2018

Study Record Updates

Last Update Posted (Actual)

April 24, 2026

Last Update Submitted That Met QC Criteria

April 22, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BLU-285-2202
  • 2017-004836-13 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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