Studie zur Beurteilung der Sicherheit und Wirksamkeit von BLU-263 bei Patienten mit indolenter und systemischer Mastozytose

Drug: Elenestinib;Drug: Placebo

Gender: All
Maximum age: N/A
Minimum age: 16 Years
Key Inclusion Criteria:

All Patients

-1. Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS)
of 0 to 2.

Part 1 and Part 2

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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 has confirmed diagnosis of ISM, confirmed by Central Pathology Review
of BM biopsy and central review of B- and C-findings by WHO diagnostic
criteria. Archival biopsy may be used if completed within the past 12 months.

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4. Patient 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 symptomatic therapies administered: H1 blockers, H2 blockers,
proton-pump inhibitors, leukotriene inhibitors, cromolyn sodium,
corticosteroids, or omalizumab.

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5. Patients must have BSC for ISM symptom management stabilized for at least 14
days prior to starting screening procedures.

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6. For patients receiving corticosteroids, the dose must be = 20 mg/d prednisone
or equivalent, and the dose must be stable for = 14 days.

Part M

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7. Patients must have mMCAS, confirmed by Central Pathology Review of BM biopsy.
An archival biopsy may be used if completed within the past 12 months.

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8. Patients must have tryptase < 20 ng/mL.

-

9. Patients must have KIT D816V in peripheral blood (PB) or BM and/or CD25+ Mast
cells in BM.

-

10. Patients must have symptoms consistent with mast cell activation (despite BSC)
in at least two organ systems characterized by cutaneous flushing, tachycardia,
syncope, hypotension, diarrhea, nausea, vomiting and gastro-intestinal
cramping) and serum blood tryptase (sBT) levels above 8 ng/mL OR Severe (Ring
and Messmer grading = II, recurrent anaphylaxis, including but not limited to
hymenoptera venom, drug or food, regardless of sBT levels.

PK Groups

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11. See inclusion criteria for All patients and Part 1/Part 2

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12. Accrual may be limited to patients who have specific disease manifestations
(ie, GI involvement) or are taking acid-reducing agents to better explore the
impact of these features on PK.

Part S:

-13. Patient has confirmed diagnosis of SSM, confirmed by Central Pathology Review of BM
biopsy and central review of B- and C-findings by WHO 2022 diagnostic criteria.

Key Exclusion Criteria:

-

1. Patient 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.

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2. Patient has been diagnosed with another myeloproliferative disorder.

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3. Patient has organ damage C-findings attributable to SM.

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4. Patient has clinically significant, uncontrolled, cardiovascular disease

-

5. Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480
msec.

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6. Patient has previously received treatment with any targeted KIT inhibitors.

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7. Patient 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.

-

8. Time since any cytoreductive therapy including mastinib 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.

- 9.Patient has received radiotherapy or psoralen and ultraviolet A (PUVA) therapy <
14 days before beginning the screening period.