(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

NCT03580655 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: BLU-285-22022017-004836-13
• Study Type: interventional
• Target: 107
• Locations: 12 countries
• Sites: 32

Brief 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)

Conditions

Systemic Mastocytosis With an Associated Hematologic Neoplasm; Advanced Systemic Mastocytosis; Aggressive Systemic Mastocytosis; Mast Cell Leukemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline through Month 65

Secondary Outcomes (21)

• Mean Change From Baseline in Advanced Systemic Mastocytosis-Symptom Assessment Form (AdvSM-SAF) Total Symptom Score (TTS)

  Baseline up to Month 6 (Cycle 6, Day 1)

• ORR Based on mIWG-MRT-ECNM Response Criteria as Assessed by Local Investigator

  Baseline through Month 19

• Time-to-Response (TTR)

  Baseline through Month 65

• Duration of Response (DOR)

  Baseline through Month 65

• Progression-free Survival (PFS)

  Baseline through Month 65

Study Arms (1)

Avapritinib

EXPERIMENTAL

Avapritinib will be administered as an immediate release tablet, orally, continuously, in 28-day cycles

Drug: Avapritinib

Interventions

Avapritinib DRUG

Avapritinib tablet

Also known as: BLU-285

Avapritinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.
• 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.

Sponsors & Collaborators

• Blueprint Medicines Corporation: lead

Study Sites (32)

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Medizinische Universität Wien, Universitätsklinik für Innere Medizin I, Klinische Abteilung für Hämatologie und Hämostaseologie

Vienna, 1090, Austria

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Odense University Hospital, Department of Haematology

Odense, DK-5000, Denmark

Location

Hôpital Necker-Enfants Malades

Paris, 75015, France

Location

CHU Toulouse - Hôpital Larrey

Toulouse, 31059, France

Location

Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltranslplantation

Aachen, 52074, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie

Hamburg, 20246, Germany

Location

Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, lnternistische Onkologie, Hämostaseologie

Leipzig, 04103, Germany

Location

Universitätsmedizin Mannheim III. Medizinische Klinik

Mannheim, 68167, Germany

Location

Klinik und Poliklinik für Innere Medizin III, Klinikum rechts der Isar der TU München

Munich, 81675, Germany

Location

Azienda Ospedaliero-Universitaria Careggi, CRIMM - Centro di Ricerca ed Innovazione per le Malattie Mieloproliferative

Florence, 50134, Italy

Location

A.O. OO.RR. S.Giovanni di Dio e Ruggi d'Aragona, University of Salerno

Salerno, 84131, Italy

Location

Centro Ricerche Cliniche di Verona - Azienda Ospedaliera Universitaria Integrata di Verona

Verona, 37134, Italy

Location

University Medical Center Groningen (UMCG)

Groningen, 9713 GZ, Netherlands

Location

Oslo University Hospital-Rikshospitalet, Hematology

Oslo, 0372, Norway

Location

Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii

Gdansk, 80-214, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu, Klinice Hematologii, Nowotworów Krwi i Transplantacji Szpiku

Wroclaw, 50-367, Poland

Location

lnstituto de Estudios de Mastocitosis de Castilla la Mancha, Hospital Virgen del Valle - Complejo Hospitalario de Toledo

Toledo, 45071, Spain

Location

Beatson West of Scotland Cancer Centre - NHS Greater Glasgow and Clyde

Glasgow, G12 0YN, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Related Publications (3)

• Reiter 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.

  PMID: 35790816 DERIVED

• Reiter 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.

  PMID: 35640224 DERIVED

• Gotlib 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.

  PMID: 34873345 DERIVED

MeSH Terms

Conditions

Mastocytosis, Systemic; Leukemia, Mast-Cell

Interventions

avapritinib

Condition Hierarchy (Ancestors)

Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mast Cell Activation Disorders; Immune System Diseases; Leukemia; Leukemia, Myeloid, Acute; Leukemia, Myeloid; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

Compared to investigator-assessed response with its challenging interpretations of any differences in ORR by central adjudication, ORR by centrally adjudicated mIWG-MRT-ECNM criteria as assessed by the study steering committee is the most accurate and reliable evaluation of response to treatment in AdvSM.

Results Point of Contact

• Title: Blueprint Medicines Medical Information
• Organization: Blueprint Medicines

medinfo@blueprintmedicines.com

1-888-258-7768

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: July 9, 2018
• Study Start: November 21, 2018
• Primary Completion: December 18, 2024
• Study Completion: December 18, 2024
• Last Updated: April 24, 2026
• Results First Posted: April 24, 2026

Record last verified: 2026-04

Locations

GB (2); ES (1); US (12); AU (1); IT (3); DK (1); CA (1); NL (1); NO (1); FR (2); DE (5); PL (2)