Overview
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.
Eligibility
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.
