Granted Patent B2

US 12,630,560 · App. 18/735,898 · Granted May 19, 2026

Inventors: Sibao Chen (East Greenwich, RI); Christopher G. F. Cooper (Rehoboth, MA); Baudouin Gerard (Arlington, MA); Joshua Courtney Horan (Somerville, MA); Jason T. Kropp (Westford, MA); Benjamin Stephen Lane (Lynnfield, MA); David James Pearson (Derby, GB)

Assignee: Nuvalent, Inc.

C07D491/22A61K9/2013A61K9/2018A61K9/2054A61K9/2059A61K9/2833C07B2200/13

Abstract

Claims (41)

1 . A method of treating cancer, comprising administering a therapeutically effective amount of a solid form comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof:

to a subject having the cancer, wherein:

(a) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.7, 15.0, and 21.2° 2θ±0.2° 2θ;

(b) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 8.6, 14.0, and 20.8° 2θ±0.2° 2θ;

(c) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 13.4, 19.5, and 20.9° 2θ±0.2° 2θ;

(d) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 12.1, 12.7, and 18.4° 2θ±0.2° 2θ;

(e) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.5, 10.8, and 21.9° 2θ±0.2° 2θ;

(f) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 8.6, 18.7, and 20.5° 2θ±0.2° 2θ;

(g) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 12.5, 13.4, and 14.6° 2θ±0.2° 2θ;

(h) the solid form comprises a besylate salt of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 15.0, 17.9 and 23.0° 2θ±0.2° 2θ; or

(i) the solid form comprises a phosphate salt of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.8, 18.5, and 24.8° 2θ±0.2° 2θ;

wherein the cancer is a ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) positive cancer.

2 . The method of claim 1 , wherein the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.7, 15.0, and 21.2° 2θ±0.2° 2θ.

3 . The method of claim 2 , wherein the XRPD pattern further comprises peaks at 17.4 and 21.3° 2θ±0.2° 2θ.

4 . The method of claim 3 , wherein the XRPD pattern further comprises peaks at 12.0, 12.2, and 13.9° 2θ±0.2° 2θ.

5 . The method of claim 2 , wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern depicted in FIG. 1 .

6 . The method of claim 2 , wherein the solid form exhibits an endothermic event, as characterized by DSC, with an onset temperature at 265° C.±2° C. and/or a peak temperature at 267° C.±2° C.

7 . The method of claim 2 , wherein the solid form is characterized by a DSC thermogram that matches the DSC thermogram depicted in FIG. 3 .

8 . The method of claim 2 , wherein the solid form exhibits a weight increase of about 0.25% when subjected to an increase in relative humidity from about 0 to about 90% relative humidity.

9 . The method of claim 2 , wherein the solid form has approximately unit cell dimensions of: a=8.4 Å, b=8.4 Å, c=14.9 Å, α=90°, β=106°, and γ=90°.

10 . The method of claim 1 , wherein the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 8.6, 14.0, and 20.8° 2θ±0.2° 2θ.

11 . The method of claim 1 , wherein the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 13.4, 19.5, and 20.9° 2θ±0.2° 2θ.

12 . The method of claim 1 , wherein the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 12.1, 12.7, and 18.4° 2θ±0.2° 2θ.

13 . The method of claim 1 , wherein the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.5, 10.8, and 21.9° 2θ±0.2° 2θ.

14 . The method of claim 1 , wherein the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 8.6, 18.7, and 20.5° 2θ±0.2° 2θ.

15 . The method of claim 1 , wherein the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 12.5, 13.4, and 14.6° 2θ±0.2° 2θ.

16 . The method of claim 15 , wherein the XRPD pattern further comprises peaks at 20.9 and 22.8° 2θ±0.2° 2θ.

17 . The method of claim 16 , wherein the XRPD pattern further comprises peaks at 11.4 and 15.8° 2θ±0.2° 2θ.

18 . The method of claim 15 , wherein the solid form is characterized by an XRPD pattern that matches the XRPD pattern depicted in FIG. 19 .

19 . The method of claim 15 , wherein the solid form has approximately unit cell dimensions of: a=8.0 Å, b=14.8 Å, c=18.0 Å, α=90°, β=90°, and γ=90°.

20 . The method of claim 1 , wherein the solid form comprises a besylate salt of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 15.0, 17.9 and 23.0° 2θ±0.2° 2θ.

21 . The method of claim 1 , wherein the solid form comprises a phosphate salt of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.8, 18.5, and 24.8° 2θ±0.2° 2θ.

22 . The method of claim 1 , comprising administering to the subject a pharmaceutical composition comprising the solid form and a pharmaceutically acceptable excipient.

23 . The method of claim 2 , comprising administering to the subject a pharmaceutical composition comprising the solid form and a pharmaceutically acceptable excipient.

24 . The method of claim 15 , comprising administering to the subject a pharmaceutical composition comprising the solid form and a pharmaceutically acceptable excipient.

25 . The method of claim 1 , wherein the cancer is a solid tumor.

26 . The method of claim 1 , wherein the cancer is a hematologic malignancy.

27 . The method of claim 1 , wherein the cancer is lung cancer, glioblastoma, inflammatory myofibroblastic tumor (IMT), bile duct cancer, ovarian cancer, gastric cancer, colorectal cancer, angiosarcoma, melanoma, epithelioid hemangioendothelioma, esophageal cancer, kidney cancer, breast cancer, colon cancer, thyroid cancer, spitzoid tumor, cholangiocarcinoma, neuroblastoma, anaplastic large cell lymphoma (ALCL), diffuse large B-cell lymphoma (DLBCL), or large B-cell lymphoma.

28 . The method of claim 1 , wherein the cancer is lung cancer.

29 . The method of claim 1 , wherein the cancer is non-small cell lung cancer.

30 . The method of claim 1 , wherein the cancer is spitzoid melanoma, esophageal squamous cell carcinoma, renal medullary carcinoma, renal cell carcinoma, papillary thyroid cancer, or serous ovarian carcinoma.

Assignments (4)

Continuity (3)

References Cited (400)