TriangleNCT03580655 · CITED IN SOURCE DOCUMENTS
(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
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2026-04-24
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)
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
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
Mean Change From Baseline in Advanced Systemic Mastocytosis-Symptom Assessment Form (AdvSM-SAF) Total Symptom Score (TTS)
ORR Based on mIWG-MRT-ECNM Response Criteria as Assessed by Local Investigator
Time-to-Response (TTR)
Duration of Response (DOR)
Progression-free Survival (PFS)
Overall Survival (OS)
Objective Response Rate
Clinical Benefit Rate
Percent Change From Baseline in Bone Marrow Mast Cells
Percent Change From Baseline in Serum Tryptase
Percent Change From Baseline in V-kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog Aspartate 816 Valine (KIT D816V) Mutation Burden
Percent Change From Baseline in Liver Volume by Imaging
Percent Change From Baseline in Spleen Volume by Imaging
Mean Change From Baseline in AdvSM-SAF Skin and Gastrointestinal Domain Scores at Month 10
Mean Change From Baseline in AdvSM-SAF Individual Symptom Scores (Severity) at Month 10
Mean Change From Baseline in AdvSM-SAF Individual Symptom Scores (Episodes) at Month 10
Change From Baseline in Patient's Global Impression of Symptom Severity (PGIS)
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAE)
Maximum Plasma Concentration (Cmax) of a Single Dose of Avapritinib
Correlation Between TSS and Serum Tryptase
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Avapritinib will be administered as an immediate release tablet, orally, continuously, in 28-day cycles
- intervention Names
- Drug: Avapritinib
- label
- Avapritinib
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Avapritinib
- description
- Avapritinib tablet
- name
- Avapritinib
- other Names
- BLU-285
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 107
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- 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
- secondary Outcomes
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- ORR Based on mIWG-MRT-ECNM Response Criteria as Assessed by Local Investigator
- time Frame
- Baseline through Month 19
- description
- 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.
- measure
- Time-to-Response (TTR)
- time Frame
- Baseline through Month 65
- description
- 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.
- measure
- Duration of Response (DOR)
- time Frame
- Baseline through Month 65
- description
- 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.
- measure
- Progression-free Survival (PFS)
- time Frame
- Baseline through Month 65
- description
- 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.
- measure
- Overall Survival (OS)
- time Frame
- Baseline through Month 65
- description
- 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).
- measure
- Objective Response Rate
- time Frame
- Baseline through Month 65
- description
- 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.
- measure
- Clinical Benefit Rate
- time Frame
- Baseline through Month 65
- description
- 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.
- measure
- Percent Change From Baseline in Bone Marrow Mast Cells
- time Frame
- Baseline up to Month 65
- description
- Blood samples were collected to characterize the change in serum tryptase concentration during treatment with avapritinib. Each cycle is 28 days long.
- measure
- Percent Change From Baseline in Serum Tryptase
- time Frame
- Baseline up to Month 65
- description
- Bone marrow aspirate and PB samples were collected to characterize the KIT D816V mutation allele fraction. Each cycle is 28 days long.
- measure
- 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
- description
- 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.
- measure
- Percent Change From Baseline in Liver Volume by Imaging
- time Frame
- Baseline up to Month 65
Full study description
- 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)
Source references
- references
- citation
- 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.
- pmid
- 41604606
- type
- DERIVED
- citation
- 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
- type
- DERIVED
- citation
- 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
- type
- DERIVED
- citation
- 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
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- rom onset of response. 22 (61%) 20 (59%) 14.2 Advanced Systemic Mastocytosis The efficacy of AYVAKIT was demonstrated in EXPLORER (NCT02561988) and PATHFINDER (NCT03580655), two multi-center, single-arm, open-label clinical trials. Response-evaluable patients include those with a confirmed diagnosis of AdvSM per World Health Orga
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Preserved source evidence · Not medical advice