(PIONEER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, Versus Placebo in Patients With Indolent Systemic Mastocytosis

Blueprint Medicines

Status and phase: Active, not recruiting; Phase 2

Conditions: Indolent Systemic Mastocytosis

Treatments: Drug: Placebo; Drug: Avapritinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03731260

2018-000588-99 (EudraCT Number)

BLU-285-2203

Details and patient eligibility

About

This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of avapritinib + best supportive care (BSC) with placebo + BSC in patients with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by BSC. The study will be conducted in 3 parts. All patients will receive treatment with avapritinib during Part 3 including those rolling over from the placebo group.

Enrollment: 251 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• 1. Patient must have SM, confirmed by Central Pathology Review of BM biopsy, and central review of B- and C-findings by WHO diagnostic criteria.
• 2. Patient must have moderate-to-severe symptoms based on minimum mean total symptom score (TSS) of the ISM Symptom Assessment Form (ISM-SAF) over the 14-day eligibility screening period.
• 3. Patient must have failed to achieve adequate symptom control for 1 or more Baseline symptoms.
• 4. For patients receiving corticosteroids, the dose must be ≤ 20 mg/d prednisone or equivalent, and the dose must be stable for ≥ 14 days.
• 5. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.

Key Exclusion Criteria:

• 1. Patient has been diagnosed with any of the following WHO SM subclassifications: cutaneous mastocytosis only, smoldering SM, SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia, or mast cell sarcoma.
• 2. Patient must not have received prior treatment with avapritinib.
• 3. Patient must not have had any cytoreductive therapy including but not limited to masitinib and midostaurin, or investigational agent for < 14 days or 5 half-lives of the drug (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 14-day ISM-SAF eligibility TSS assessment.
• 4. Patient must not have received radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.
• 5. Patient must not have received any hematopoietic growth factor the preceding 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.
• 6. Patient must not have a QT interval corrected using Fridericia's formula (QTcF) of > 480 msec.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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251 participants in 7 patient groups, including a placebo group

(Part 1) Avapritinib Dose 1 + BSC

Experimental group

Description:

Avapritinib will be administered orally in continuous 28-day cycles

Treatment:

Drug: Avapritinib

(Part 1) Avapritinib Dose 2 + BSC

Experimental group

Description:

Avapritinib will be administered orally in continuous 28-day cycles

Treatment:

Drug: Avapritinib

(Part 1) Avapritinib Dose 3 + BSC

Experimental group

Description:

Avapritinib will be administered orally in continuous 28-day cycles

Treatment:

Drug: Avapritinib

(Part 1) Placebo + BSC

Placebo Comparator group

Description:

Placebo will be administered orally in continuous 28-day cycles

Treatment:

Drug: Placebo

(Part 2) Avapritinib RP2D + BSC

Experimental group

Description:

Avapritinib will be administered orally in continuous 28-day cycles

Treatment:

Drug: Avapritinib

(Part 2) Placebo + BSC

Placebo Comparator group

Description:

Placebo will be administered orally in continuous 28-day cycles

Treatment:

Drug: Placebo

(Part 3) Avapritinib RP2D + BSC

Experimental group

Description:

Avapritinib will be administered orally in continuous 28-day cycles

Treatment:

Drug: Avapritinib