Patient case: 39-year-old female with melanoma; genetic feature: KIT (N822Y)

Clinical trial: Study of BLU-285 in Patients With Advanced Systemic Mastocytosis (advSM) and Relapsed or Refractory Myeloid Malignancies

Summary: This is a Phase 1, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of BLU-285, administered orally (PO), in adult patients with advanced systemic mastocytosis and other relapsed or refractory myeloid malignancies. The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 2).


Eligibility: Inclusion Criteria:
  For Part 1:Patients must have one of the following diagnoses:
  -  Aggressive systemic mastocytosis (ASM) as confirmed by World Heath Organization (WHO) diagnostic criteria.
  -  Systemic mastocytosis-associated hematologic non-mast cell disease (SM-AHNMD) as confirmed by WHO diagnostic criteria, and the patient also has at least 1 C-finding attributable to systemic mastocytosis (SM). The AHNMD must be myeloid, with the following exceptions that are excluded: Acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS) that is very high- or high-risk as defined by the International prognostic scoring system for myelodysplastic syndromes (IPSS-R) and Philadelphia chromosome positive malignancies.
  -  Mast cell leukemia (MCL) as confirmed per WHO diagnostic criteria.
  -  Histologically- or cytologically- confirmed myeloid malignancy as confirmed by IWG-MRT or WHO diagnostic criteria that is relapsed or refractory to standard treatments. AML, MDS that is very high- or high-risk as defined by the IPSS-R, and Philadelphia chromosome positive malignancies are excluded.
  -  Upon discussion with the sponsor, other relapsed or refractory, potentially BLU-285-responsive hematologic neoplasms (e.g., evidence of aberrant KIT or platelet derived growth factor receptor (PDGFR) signaling) may be considered for enrollment.
  For Part 2:
  -  Group 1: ASM as confirmed by WHO diagnostic criteria.
  -  Group 2: SM-AHNMD as confirmed by WHO diagnostic criteria, that also has at least 1 C-finding attributable to SM. The AHNMD must be myeloid, with the following exceptions that are excluded: AML, MDS that is very high- or high-risk as defined by the IPSS-R, and Philadelphia chromosome positive malignancies.
  -  Group 3: MCL as confirmed per WHO diagnostic criteria.
  Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
  Exclusion Criteria:
  -  QT interval corrected using Fridericia's formula (QTcF) >470 milliseconds
  -  Platelet count <25,000/mL
  -  Absolute neutrophil count <500/mL
  -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >3 x the upper limit of normal (ULN); >5 × ULN if associated with clinically suspected liver infiltration by mastocytosis or another disease for which the patient enrolled into the study
  -  Total bilirubin >1.5 × ULN; >3 × ULN if associated with liver infiltration by the disease being treated or in the presence of Gilbert's Disease
  -  Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min
  -  Brain malignancy or metastases to the brain
  -  History of a seizure disorder or requirement for anti-seizure medication
  -  Known risk of intracranial bleeding, such as a brain aneurysm or history of subdural or subarachnoid bleeding

Relevance to patient case: not relevant