Recruiting
Phase 2
Phase 3

BLU-263

Sponsor:

Blueprint Medicines Corporation

Code:

NCT04910685

Conditions

Indolent Systemic Mastocytosis

Smoldering Systemic Mastocytosis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Elenestinib

Placebo

Study Details

Brief summary:

This is a randomized, double-blind, placebo-controlled, Phase 2/3 study comparing the efficacy and safety of elenestinib (BLU-263) + symptom directed therapy (SDT) with placebo + SDT in participants with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by SDT. Parts 1 and 2 will enroll participants with ISM. Participants enrolled in Part 2 will roll over onto Part 3 to receive treatment with elenestinib in an open-label fashion following completion of the earlier Part. Part K will enroll participants with ISM who have previously received an approved selective KIT inhibitor. The study also includes pharmacokinetic (PK) groups that will enroll participants with ISM.

Conditions

Indolent Systemic Mastocytosis

Smoldering Systemic Mastocytosis

Study ID

NCT04910685

Start date

Nov 30, 2021

Status verified date

Jul, 2026

Completion date

Sep 30, 2032

Anticipated

Primary completion date

Sep 30, 2032

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key Inclusion Criteria:

All Participants:

-Participant must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.

Part 1 and PK groups:

  • Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review
  • Participant must have failed to achieve adequate symptom control for 1 or more Baseline symptoms, as determined by the Investigator, with at least 2 of the following symptom-directed therapies administered: H1 blockers, H2 blockers, proton-pump inhibitors, leukotriene inhibitors, cromolyn sodium, corticosteroids, or omalizumab.
  • Participants must have SDT for ISM symptom management stabilized for at least 14 days prior to starting screening procedures.
  • For participants receiving corticosteroids, the dose must be ≤ 20 mg/day prednisone or equivalent, and the dose must be stable for ≥ 14 days.

Part K:

-Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review

Part S:

-Participant has confirmed diagnosis of SSM, confirmed by Central Pathology Review of BM biopsy and central review of B- and C-findings by WHO diagnostic criteria.

Part 2:

-Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review

Key Exclusion Criteria:

  • Participant has been diagnosed with any of the following WHO systemic mastocytosis (SM) sub-classifications: cutaneous mastocytosis only, SM with an associated hematologic neoplasm of non-MC lineage (SM-AHN), aggressive SM, mast cell leukemia, or mast cell sarcoma.
  • Participant has been diagnosed with another myeloproliferative disorder.
  • Participant has organ damage attributable to SM.
  • Participant has clinically significant, uncontrolled, cardiovascular disease
  • Participant has a QT interval corrected using Fridericia's formula (QTcF) > > 470 milliseconds (msec) (for females) or > 450 msec (for males).
  • Participant has a history of a primary malignancy that has been diagnosed or required therapy within 3 years. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
  • Time since any cytoreductive therapy including masitinib and midostaurin should be at least 5 half-lives or 14 days (whichever is longer), and for cladribine, interferon alpha, pegylated interferon, or antibody therapy < 28 days or 5 half-lives of the drug (whichever is longer), before beginning the screening period.
  • Participant has received radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before beginning the screening period.

Other protocol-defined criteria apply.

Study Design

Enrollment

534 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: (Part 1) Elenestinib Dose 1 + SDT

Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily until completion of Part 1.

experimental: (Part 1) Elenestinib Dose 2 + SDT

Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily until completion of Part 1.

experimental: (Part 1) Elenestinib Dose 3 + SDT

Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily until completion of Part 1.

placebo comparator: (Part 1) Placebo + SDT

Participants will receive SDT and matching placebo. SDT will be determined on a per participant basis. Placebo will be administered orally, once daily until completion of Part 1.

experimental: (Part 2) Elenestinib Dose 1 + SDT

Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for approximately 48 weeks.

placebo comparator: (Part 2) Placebo + SDT

Participants will receive SDT and matching placebo. SDT will be determined on a per participant basis. Placebo will be administered orally, once daily for approximately 48 weeks.

experimental: (Part 3) Elenestinib + SDT

Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years.

experimental: (Part S) Elenestinib Dose 1 + SDT

Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years.

experimental: (Part K) Elenestinib Dose 1 + SDT

Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years.

experimental: (PK groups) Elenestinib + SDT

Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years.

Interventions

Elenestinib

Elenestinib oral tablet

Placebo

Placebo oral tablet

Primary outcome measure

  • Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to 12 weeks ]
  • Part 1: Mean change from baseline in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS) [ Time Frame: Baseline, Week 13 ]
  • Part 2: Mean change from baseline in ISM-SAF TSS [ Time Frame: Baseline, Week 49 ]
  • Part 3: Number of participants with Adverse Events (AEs) [ Time Frame: Up to 5 years ]
  • Part 3: Change from baseline in ISM-SAF TSS [ Time Frame: Baseline up to 5 years ]

Central Contacts and Locations

Central contacts

Blueprint Medicines

617-714-6707medinfo@blueprintmedicines.com

Locations

University of Alabama at Birmingham

Recruiting

Birmingham, Alabama, United States, 35294

David Geffen School of Medicine at UCLA

Recruiting

Los Angeles, California, United States, 90095

Stanford Cancer Institute

Recruiting

Palo Alto, California, United States, 94305

UCHealth Blood Disorders and Cell Therapies Center - Anschutz Medical Campus

Recruiting

Aurora, Colorado, United States, 80045

Winship Cancer Institute, Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Brigham and Women's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Michigan Medicine University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55902

Roswell Park Cancer Institute

Recruiting

Buffalo, New York, United States, 14263

Columbia University Medical Center

Recruiting

New York, New York, United States, 10032

Duke Asthma, Allergy and Airway Center

Recruiting

Durham, North Carolina, United States, 27705

University of Cincinnati Medical Center

Recruiting

Cincinnati, Ohio, United States, 45219

The University of Texas, MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Huntsman Cancer Institute, University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

More Information

Sponsor

Blueprint Medicines Corporation

Last update posted

Aug 4, 2026

Last verified

Jul, 2026

Keywords

  • ISM
  • SSM

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Blueprint Medicines Corporation on 2026-08-04.