Crystalline forms of (s)-1-(4-fluorophenyl)-1-(2-(4-(6-(1- methyl-1h-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazinyl)-pyrimidin-5-yl)ethan-1-amine and methods of making

Patent metadata

Field	Value
Publication number	US-2024132510-A1
Application number	US-202318543793-A
Country	US
Kind code	A1
Filing date	Dec 18, 2023
Priority date	Apr 12, 2019
Publication date	Apr 25, 2024
Grant date	—

Abstract

Crystalline Forms of Compound (I):

pharmaceutically acceptable salts thereof and solvates of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating disorders and conditions associated with oncogenic KIT and PDGFRA alterations using the same, and methods for making Compound (I) and crystalline forms thereof are also disclosed.

First claim

1 . A method of treating systemic mastocytosis comprising administering to a patient in need thereof a therapeutically effective amount of crystalline Form A of Compound (I):

characterized by an X-ray powder diffractogram which comprises at least three peaks at 20 angles chosen from 11.5±0.2, 15.4±0.2, 16.7±0.2, 20.0±0.2, and 21.6±0.2.

2 . The method of claim 1 , wherein the crystalline Form A of Compound (I) is characterized by an X-ray powder diffractogram which comprises at least seven peaks at 20 angles chosen from 11.5±0.2, 15.4±0.2, 16.7±0.2, 18.1±0.2, 20.0±0.2, 21.6±0.2, 23.1±0.2, 23.9±0.2, 25.9±0.2, and 30.7±0.2.

3 . The method of claim 1 , wherein the crystalline Form A of Compound (I) is characterized by an X-ray powder diffractogram which comprises at least eight peaks at 20 angles chosen from 11.5±0.2, 15.4±0.2, 16.7±0.2, 18.1±0.2, 20.0±0.2, 21.6±0.2, 23.1±0.2, 23.9±0.2, 25.9±0.2, and 30.7±0.2.

4 . The method of claim 1 , wherein the crystalline Form A of Compound (I) is characterized by an X-ray powder diffractogram which comprises peaks at 20 angles of 11.5±0.2, 15.4±0.2, 16.7±0.2, 18.1±0.2, 20.0±0.2, 21.6±0.2, 23.1±0.2, 23.9±0.2, 25.9±0.2, and 30.7±0.2.

5 . The method of claim 1 , wherein the crystalline Form A of Compound (I) is characterized by an X-ray powder diffractogram which comprises peaks at 20 angles of 11.5±0.2, 15.4±0.2, 16.7±0.2, 20.0±0.2, and 21.6±0.2.

6 . The method of claim 1 , wherein the crystalline Form A of Compound (I) is characterized by a DSC thermogram having an endothermic event with a signal at a temperature ranging from 194° C. to 195° C. or an onset temperature of 193° C.

7 . The method of claim 1 , wherein the systemic mastocytosis is smoldering systemic mastocytosis (SSM).

8 . The method of claim 1 , wherein the systemic mastocytosis is advanced systemic mastocytosis (AdvSM).

9 . The method of claim 8 , wherein 200 mg of Crystalline Form A of Compound (I) is administered to the patient once daily.

10 . The method of claim 8 , wherein the systemic mastocytosis is selected from aggressive systemic mastocytosis (ASM), systemic mastocytosis associated with hematological non-mast cell lineage disease (SM-AHN), and mast cell leukemia (MCL).

11 . The method of claim 1 , wherein the systemic mastocytosis is indolent systemic mastocytosis (ISM).

12 . The method of claim 11 , wherein the patient is identified as having a minimum total symptom score (TSS) of >28 as assessed using the indolent systemic mastocytosis-symptom assessment form (ISM-SAF).

13 . The method of claim 11 , wherein 25 mg of crystalline Form A of Compound (I) is administered to the patient once a daily.

14 . The method of claim 1 , wherein the patient has a mutation in Exon 17 in KIT.

15 . The method of claim 14 , wherein the patient has a D816 mutation in KIT in Exon 17.

16 . The method of claim 15 , wherein the D816 mutation is D816V.

17 . The method of claim 1 , wherein 25 mg of the crystalline Form A of Compound (I):

is administered to the patient once daily.

Assignees

• Blueprint Medicines Corp

Inventors

• Waetzig Joshua D
• Mar Brenton
• Wilkie Gordon

Classifications

• A61K31/155 Primary

  Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2) · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title