University Medical Centre Mannheim 68167 Mannheim (Baden-Württemberg) GermanyRekrutierend» Google-MapsStanford Cancer Institute 94305 Palo Alto United StatesNoch nicht rekrutierend» Google-MapsDana-Farber Cancer Institute 02215 Boston United StatesRekrutierend» Google-Maps
University of Michigan 48109 Ann Arbor United StatesRekrutierend» Google-MapsHuntsman Cancer Institute 84112 Salt Lake City United StatesRekrutierend» Google-MapsAntwerp University Hospital 2650 Edegem BelgiumRekrutierend» Google-MapsUniversity Hospital Ghent 9000 Ghent BelgiumRekrutierend» Google-MapsCHU Caen - Institut d'Hematologie de Basse Normandie 14033 Caen FranceRekrutierend» Google-MapsMaastricht University Medical Center 6229 HX Maastricht NetherlandsRekrutierend» Google-MapsOslo University Hospital 0450 Oslo NorwayRekrutierend» Google-MapsInstituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast) 45071 Toledo SpainRekrutierend» Google-Maps
1. Dose Escalation: Number of Dose-limiting Toxicities (DLTs) (monotherapy only) (Time Frame - 28 Days): Monotherapy: The Recommended Dose (RD) will be primarily determined by the number of DLTs in the first 28 days of treatment with elenestinib (BLU-263) monotherapy.
2. Dose Escalation: Number of DLTs (combination therapy only) (Time Frame - 28 Days): Combination therapy: The RD will be primarily determined by the number of DLTs (during 28 days starting from Day 15 of C1 or Day 15 of C2) with elenestinib (BLU-263) in combination with azacitidine.
3. Dose Escalation and Expansion: Pure Pathological Response (PPR) Rate for SM in Selective KIT Inhibitor-naïve Participants (monotherapy only) (Time Frame - Up to approximately 4 years): PPR Rate is defined as complete remission (resolution of palpable splenomegaly/hepatomegaly) (CR) + complete remission with partial recovery of peripheral blood counts (CRh) + partial remission (≥35% reduction in spleen volume) (PR)
4. Dose Escalation and Expansion: Number of Participants with Adverse Events (AEs) (Time Frame - Up to approximately 4 years)
5. Dose Escalation and Expansion: Number of Participants with Serious Adverse Events (SAEs) (Time Frame - Up to approximately 4 years)
Secondary outcome:
1. Dose Escalation and Expansion: Overall Response Rate (ORR) for AdvSM using modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG-MRT-ECNM) (monotherapy only) (Time Frame - Up to approximately 4 years): ORR is defined as CR + CRh + PR + Clinical Improvement (CI)
2. Dose Escalation and Expansion: ORR for SM Using Modified IWG-MRT-ECNM (combination therapy only) (Time Frame - Up to approximately 4 years)
3. Dose Escalation and Dose Expansion: Maximum Plasma Concentration (Cmax) of BLU-263 (Time Frame - Up to approximately 4 years)
4. Dose Escalation and Dose Expansion: Cmax of Azacitidine (combination therapy only) (Time Frame - Up to approximately 4 years)
5. Dose Escalation and Dose Expansion: Time to Maximum Concentration (Tmax) of BLU-263 (Time Frame - Up to approximately 4 years)
6. Dose Escalation and Dose Expansion: Tmax of Azacitidine (combination therapy only) (Time Frame - Up to approximately 4 years)
7. Dose Escalation and Dose Expansion: Area Under the Curve From Time Zero to 24 Hours (AUC(0-24)) of BLU-263 (Time Frame - Up to approximately 4 years)
8. Dose Escalation and Dose Expansion: AUC(0-24) of Azacitidine (combination therapy only) (Time Frame - Up to approximately 4 years)
9. Dose Escalation and Dose Expansion: Apparent Volume of Distribution (Vz/F) of BLU-263 (Time Frame - Up to approximately 4 years)
10. Dose Escalation and Dose Expansion: Vz/F of Azacitidine (combination therapy only) (Time Frame - Up to approximately 4 years)
11. Dose Escalation and Dose Expansion: Terminal Elimination Half-life (t1/2) of BLU-263 (Time Frame - Up to approximately 4 years)
12. Dose Escalation and Dose Expansion: t1/2 of Azacitidine (combination therapy only) (Time Frame - Up to approximately 4 years)
13. Dose Escalation and Dose Expansion: Apparent Oral Clearance (CL/F) of BLU-263 (Time Frame - Up to approximately 4 years)
14. Dose Escalation and Dose Expansion: CL/F of Azacitidine (combination therapy only) (Time Frame - Up to approximately 4 years)
15. Dose Escalation and Dose Expansion: Accumulation Ratio of BLU-263 (Time Frame - Up to approximately 4 years)
16. Dose Escalation and Dose Expansion: Accumulation Ratio of Azacitidine (combination therapy only) (Time Frame - Up to approximately 4 years)
17. Dose Escalation and Expansion: Overall Survival (OS) (monotherapy only) (Time Frame - Up to approximately 4 years)
18. Dose Escalation and Expansion: Time to Response (TtR) (monotherapy only) (Time Frame - Up to approximately 4 years)
19. Dose Escalation and Expansion: Duration of Response (DOR) (monotherapy only) (Time Frame - Up to approximately 4 years)
20. Dose Escalation and Expansion: Progression-Free Survival (PFS) (monotherapy only) (Time Frame - Up to approximately 4 years)
21. Dose Escalation and Expansion: Proportion of Participants Pursuing Stem Cell Transplant (monotherapy only) (Time Frame - Up to approximately 4 years)
22. Dose Escalation and Expansion: PPR Rate for SM (combination therapy only) (Time Frame - Up to approximately 4 years)
Experimental: Monotherapy Participants with AdvSM (ASM, SM-AHN, or MCL) will receive BLU-263 monotherapy.
Experimental: Combination therapy Participants with high risk and very high risk systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) of non-MC lineage will receive BLU-263 in combination with azacitidine.