EGFR INHIBITORS

1 . A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein

X 1 is S and X 2 is N or X 1 is N and X 2 is S;

X is CR x or N;

R x is H, F, or —O—R 1 ;

R 1 is C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or 4- to 12-membered heterocyclyl, wherein the alkyl, cycloalkyl, and heterocyclyl represented by R 1 are optionally substituted with 1 to 4 groups independently selected from deuterium, halo, C 1 -C 4 alkyl, ═O (as valence permits), —OR 1c , CN, NR 1a R 1b , C 3 -C 6 cycloalkyl, and 4- to 8-membered heterocyclyl, wherein the alkyl is optionally substituted with 1 to 3 groups selected from halo, deuterium, and OR 1a and NR 1a R 1b , and the heterocyclyl and C 3 -C 6 cycloalkyl are each optionally substituted with 1 to 4 groups selected from ═O, NR 1a R 1b , and C 1 -C 4 alkyl optionally substituted with NR 1a R 1b ,

L 10 -R 10 is halo; or

L 10 is a bond, NH, —NHC(O)—*, —NHC(O)O—*, O, or —OC(O)—*; wherein —* represents the point which attaches to R 10 ; and

R 10 is H; or

C 1 -C 4 alkyl optionally substituted with 1 to 4 groups independently selected from halo, deuterium, OR 1a , NR 1a R 1b , C 3 -C 6 cycloalkyl, 4- to 12-membered heterocyclyl and 5 to 10 membered heteroaryl, wherein the heterocyclyl and heteroaryl are each optionally substituted with 1 to 4 groups independently selected from halo, deuterium, ═O, NR 1a R 1b , and C 1 -C 4 alkyl; or

C 3 -C 8 cycloalkyl, phenyl, 4- to 12-membered heterocyclyl, or 5- to 12-membered heteroaryl, wherein the cycloalkyl, phenyl, heterocyclyl and heteroaryl represented by R 10 are each optionally substituted with 1 to 4 groups independently selected from R 11 ;

each R 11 is independently selected from halo, deuterium, OR 1a , C(O)R 1a , C(O)NR 1a R 1b , NR 1a C(O)OR 1a , NR 1a R 1b , S(O) 2 R 1a , C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, phenyl, 4- to 12-membered heterocyclyl and 5- to 12-membered heteroaryl, wherein the alkyl, cycloalkyl, phenyl, heterocyclyl and heteroaryl represented by R 11 are each optionally substituted with 1 to 4 groups selected from deuterium, halo, C 1 -C 4 alkyl, OR 1a and NR 1a R 1b , or two R 1 which are attached to the same carbon atom are taken together to form ═O;

R 2 is halo, NR 1a R 1b , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkenyloxy, C 2 -C 4 alkynyloxy, C 3 -C 8 cycloalkyl, 4- to 12-membered heterocyclyl, phenyl, or 5- or 12-membered heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, cycloalkyl, heterocycyl, phenyl, and heteroaryl represented by R 2 are each optionally substituted with 1 to 4 groups represented by R 2a ; and R 2a is selected from deuterium, halo, ═O (as valence permits), OR 1c , NR 1a R 1b , C(O)R 1c , C(O)OR 1c , —S(O) 2 R 1c , C 1 -C 4 alkyl, and 4- to 12-membered heterocyclyl, wherein the C 1 -C 4 alkyl and C 1 -C 4 alkoxy groups represented by R 2a are each optionally substituted with 1 to 4 groups selected from deuterium, halo, OH, and C 1 -C 4 alkoxy, and the 4- to 12-membered heterocyclyl represented by R 2a is optionally substituted with 1 to 4 groups independently selected from halo, deuterium, ═O, NR 1a R 1b , and C 1 -C 4 alkyl;

R 1a is H, deuterium, C 1 -C 4 alkyl, or C 3 -C 6 cycloalkyl;

R 1b is H, deuterium, C 1 -C 4 alkyl, or C 3 -C 6 cycloalkyl;

R 1c is H, deuterium, C 1 -C 4 alkyl optionally substituted with 1 to 3 halo, or C 3 -C 6 cycloalkyl;

R 3a is H, deuterium, halo, OH, C 1-4 alkyl, or C 1 -C 4 alkoxy;

R 3b is H, deuterium, halo, OH, C 1-4 alkyl, or C 1 -C 4 alkoxy;

R 3c is H, deuterium, halo, OH, C 1-4 alkyl, or C 1 -C 4 alkoxy;

R 4 is H, deuterium or halo; and

R 5 is H or deuterium.

2 . The compound of claim 1 having Formula (II):

or a pharmaceutically acceptable salt thereof.

3 . The compound of claim 2 having Formula (III):

or a pharmaceutically acceptable salt thereof, wherein

L 10 -R 10 is H or halo;

R 3a is H, deuterium, or halo;

R 3b is H, deuterium, or halo; and

R 3c is H, deuterium, or halo.

4 . The compound of claim 1 , having Formula (III-A):

or a pharmaceutically acceptable salt thereof.

5 . The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein:

(i) R 1 is C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or 4- to 8-membered heterocyclyl, wherein the alkyl, cycloalkyl, and heterocyclyl represented by R 1 are optionally substituted with 1 to 4 groups independently selected from halo, CN, ═O, NR 1a R 1b , C 1 -C 4 alkyl (optionally substituted with 1 to 4 groups selected from halo, —OH and C 1 -C 4 alkoxy), —OH, C 1 -C 4 alkoxy, NR 1a R 1b , C 3 -C 6 cycloalkyl, and 4- to 8-membered heterocyclyl (optionally substituted with ═O, NR 1a R 1b , and/or C 1 -C 4 alkyl);

(ii) R 1 is:

C 1 -C 6 alkyl optionally substituted with 1 or 4 groups selected from halo, CN, ═O, NHCH 3 , N(CH 3 ) 2 , OH, C 1 -C 4 alkoxy, C 3 -C 4 cycloalkyl, and 4- to 8-membered heterocyclyl (optionally substituted with 1 to 4 groups selected from ═O, NR 1a R 1b , and/or C 1 -C 4 alkyl optionally substituted with NR 1a R 1b );

C 3 -C 6 cycloalkyl optionally substituted with 1 or 2 groups selected from C 1 -C 4 alkyl, OH, NH 2 , NHCH 3 , and N(CH 3 ) 2 ;

4- to 6-membered heterocyclyl optionally substituted with 1 or 3 groups selected from halo, C 1 -C4 alkyl (optionally substituted with 1 to 4 groups selected from halo, —OH and C 1 -C 4 alkoxy), ═O, OH, C 1 -C 4 alkoxy, oxetanyl, and tetrahyropyranyl; or

(iii) R 1 is:

C 1 -C 4 alkyl optionally substituted with 1 or 2 groups selected from N(CH 3 ) 2 , ═O, azetidinyl, oxetanyl, and morpholinyl;

oxetanyl;

pyrrolidinyl optionally substituted with 1 or 2 groups selected from methyl and ═O; or

piperidinyl optionally substituted with F or oxetanyl.

6 - 7 . (canceled)

8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein;

(i) R 2 is;

C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, 4- to 10-membered heterocyclyl, phenyl, or 5- or 6-membered heteroaryl,

wherein the alkyl, alkenyl, alkynyl, and alkoxy represented by R 2 are each optionally substituted with 1 to 4 groups selected from deuterium, halo, ═O (as valence permits), OH, NR 1a R 1b , C(O)R 1c , C(O)OR 1c , —S(O) 2 R 1c , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, and 4- to 6-membered heterocyclyl (optionally substituted with ═O, NR 1a R 1b , C 1 -C 4 alkyl);

wherein the 4- to 10-membered heterocycyl, phenyl, and 5- or 6-heteroaryl represented by R 2 are each optionally substituted with 1 to 4 groups selected from deuterium, halo, ═O (as valence permits), OH, NR 1a R 1b , C(O)R 1c , C(O)OR 1c , —S(O) 2 R 1c , C 1 -C 4 alkyl (optionally substituted with 1 to 4 groups selected from halo, —OH and C 1 -C 4 alkoxy), C 1 -C 4 alkoxy (optionally substituted with 1 to 4 groups selected from halo and —OH), and 4- to 6-membered heterocyclyl (optionally substituted with 1 to 2 groups selected from ═O, NR 1a R 1b , C 1 -C 4 alkyl);

(ii) R 2 is:

C 1 -C 4 alkoxy optionally substituted with 1 to 4 groups selected from deuterium, halo, ═O (as valence permits), C 1 -C 4 alkoxy, and 4- to 6-membered heterocyclyl (optionally substituted with ═O, NR 1a R 1a , C 1 -C 4 alkyl)

C 2 -C 4 alkynyl optionally substituted with 1 to 2 groups selected from C 1 -C 4 alkyl and 4- to 6-membered heterocyclyl (optionally substituted with ═O, NR 1a R 1b , C 1 -C 4 alkyl);

4- to 10-membered heterocyclyl, phenyl, or 5- or 6-membered heteroaryl each optionally substituted with 1 to 4 groups selected from halo, ═O (as valence permits), C 1 -C 4 alkyl (optionally substituted with 1 to 4 groups selected from halo, —OH and C 1 -C 4 alkoxy), C 1 -C 4 alkoxy (optionally substituted with 1 to 4 groups selected from halo and —OH), —C(O)OC 1 -C 4 alkyl, —S(O) 2 C 1 -C 4 alkyl, and 4- to 6-membered heterocyclyl (optionally substituted with 1 to 2 groups selected from ═O, NR 1a R 1b , C 1 -C 4 alkyl);

(iii) R 2 is:

C 1 -C 4 alkoxy optionally substituted with 1 to 3 groups selected from deuterium, OCH 3 , and piperizinyl (optionally substituted with methyl);

C 2 -C 4 alkynyl optionally substituted with 4- to 6-membered heterocyclyl (optionally substituted with C 1 -C 2 alkyl);

1,3-dihydro-2H-imidazol-2-onyl optionally substituted with 1 or 2 C 1 -C 2 alkyl;

2,5 -diazabicyclo[4.1.0]heptanyl optionally substituted with C 1 -C 2 alkyl;

6-oxa-3-azabicyclo[3.1.1]heptanyl;

2-oxa-6 -azaspiro[3.3]heptanyl;

dihydro-3H-pyrazol-3-onyl optionally substituted with 1 or 2 groups selected from C 1 -C 3 alkyl (optionally substituted with 1 to 3 halo);

hexahydro-1H-2 -pyrrolo[2,1-c]pyrazinyl;

imidazolidinyl optionally substituted with 1 or 2 groups selected from ═O and C 1 -C 3 alkyl;

morpholinyl optionally substituted with 1 or 2 groups selected from C 1 -C 3 alkyl;

phenyl optionally substituted with S(O) 2 CH 3 ;

piperizinyl optionally substituted with 1 or 3 groups selected from C 1 -C 3 alkyl (optionally substituted with —OH or C 1 -C 2 alkoxy) and —C(O)OC 1 -C 4 alkyl;

pyrazolyl optionally substituted with 1 or 2 groups selected from piperizinyl (optional substituted with methyl), piperidinyl (optionally substituted with methyl), C 1 -C 4 alkyl, and C 1 -C 4 alkoxy, wherein the C 1 -C 4 alkyl and C 1 -C 4 alkoxy are each optionally substituted with 1 to 4 groups selected from halo and OH;

pyrrolidinyl optionally substituted with 1 or 2 groups selected from C 1 -C 3 alkyl (optionally substituted with —OH) and C 1 -C 2 alkoxy; or

triazolyl optionally substituted with C 1 -C 3 alkyl; or

(iv) R 2 is:

pyrazolyl optional substituted with 1 or 2 groups selected from methyl, methoxy, —OCHF 2 , —CH 2 C(OH)(CH 3 ) 2 , —CH(CH 3 )CH 2 OH, and —C(CH 3 ) 2 CH 2 OH;

pyrrolidinyl optionally substituted with 1 or 2 groups selected from methoxy and —C(OH)(CH 3 ) 2 ;

6-oxa-3-azabicyclo[3.1.1]heptanyl; or

2-oxa-6 -azaspiro[3.3]heptanyl.

9 - 11 . (canceled)

12 . The compound of claim 2 having the Formula (IV):

or a pharmaceutically acceptable salt thereof, wherein

R x is H, F;

R 3a is H, deuterium, or halo;

R 3b is H, deuterium, or halo; and

R 3c is H, deuterium, or halo.

13 . The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein L 10 is a bond, NH, —NHC(O)—*, or O; wherein —* represents the point which attaches to R 10 .

14 . The compound of claim 13 , or a pharmaceutically acceptable salt thereof, wherein

L 10 -R 10 is H or halo; or

R 10 is:

C 1 -C 4 alkyl optionally substituted with 1 to 4 groups independently selected from halo, OR 1a , NR 1a R 1b , 4 to 6 membered heterocyclyl wherein the 4 to 6 membered heterocyclyl is optionally substituted with 1 to 2 groups independently selected from halo, ═O, NR 1a R 1b , and C 1 -C 4 alkyl; or

4- to 8-membered heterocyclyl optionally substituted with 1 to 2 groups selected from halo, ═O, C 1 -C 4 alkyl, OR 1a , C(O)R 1a ; C(O)NR 1a R 1b , NR 1a C(O)OR 1a , and NR 1a R 1b ; or

5- to 6-membered heteroaryl optionally substituted with 1 to 2 groups selected from halo, C 1 -C 4 alkyl, OR 1a , C(O)R 1a ; C(O)NR 1a R 1b , NR 1a C(O)OR 1a , NR 1a R 1b , and 4- to 6-membered heterocyclyl (which is further optionally substituted with 1 or 2 groups selected from halo, ═O, NR 1a R 1b , and C 1 -C 4 alkyl).

15 . The compound of claim 14 , or a pharmaceutically acceptable salt thereof, wherein L 10 -R 10 is H or halo.

16 . The compound of claim 14 , or a pharmaceutically acceptable salt thereof, wherein:

(i) L 10 is a bond; and

R 10 is 5- to 6-membered heteroaryl optionally substituted with C 1 -C 2 alkyl or 4- to 6-membered heterocyclyl (which is further optionally substituted with 1 or 2 groups selected from halo and C 1 -C 2 alkyl) (e.g., pyrazolyl optionally substituted with methyl or piperidinyl (optionally substituted with 1 or 2 groups selected from F and methyl);

(ii) L 10 is NH; and

R 10 is 4- to 6-membered heterocyclyl optionally substituted with 1 to 2 groups selected from halo, C 1 -C 2 alkyl, and —C(O)C 1 -C 2 alkyl (e.g., piperidinyl optionally substituted with 1 or 2 groups selected from F, methyl, and —C(O)CH 2 CH 3 );

(iii) L 10 is —NHC(O)—*, wherein —* represents the point which attaches to R 10 , and R 10 is:

C 1 -C 2 alkyl optionally substituted with 4 to 6 membered heterocyclyl (e.g., ethyl optionally substituted with piperidinyl); or

4- to 8-membered heterocyclyl optionally substituted with 1 to 2 groups selected from halo, C 1 -C 2 alkyl, and —C(O)C 1 -C 2 alkyl (e.g., azetidinyl optionally substituted with methyl, piperidinyl optionally substituted with 1 or 2 groups selected from methyl and fluoro, piperizinyl optionally substituted with 1 or 2 groups selected from methyl and ethyl, octahydropyrrolo[3,4-b]pyrrolyl optionally substituted with methyl); or

(iv) L 10 is O; and

R 10 is:

C 1 -C 2 alkyl (e.g., CH 3 ); or

4- to 6-membered heterocyclyl optionally substituted with 1 to 2 groups selected from halo, C 1 -C 2 alkyl, and —C(O)C 1 -C 2 alkyl (e.g., tetrohydrofuranyl, tetrohydropyranyl, or piperidinyl optionally substituted with —C(O)CH 2 CH 3 ).

17 - 19 . (canceled)

20 . The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein;

(i) R 2 is C 1 -C 4 alkyl or 5- or 6-membered heteroaryl (e.g., 5-membered heteroaryl), wherein the heteroaryl represented by R 2 is optionally substituted with 1 to 4 groups selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, and 4 to 6 membered heterocyclyl (optionally substituted with C 1 -C 4 alkyl); or

(ii) R 2 is methyl or pyrazolyl optionally substituted with 1 or 2 groups selected from methyl, methoxy, and piperidinyl (optionally substituted with methyl).

21 . (canceled)

22 . The compound of claim 12 , or a pharmaceutically acceptable salt thereof wherein R x is H.

23 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 3a is H or halo; R 3b and R 3c are H; and R 4 and R 5 are H.

24 . (canceled)

25 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 1a is H or C 1 -C 4 alkyl; R 1b is H or C 1 -C 4 alkyl; and R 1c is H or C 1 -C 4 alkyl optionally substituted with 1 to 3 halo (F).

26 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

27 . A method of treating a cancer, comprising administering a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

28 . The method of claim 27 , wherein the cancer is non-small cell lung cancer; or wherein the cancer in the subject in need thereof has metastasized.

29 . (canceled)

30 . The method of claim 27 , wherein the cancer is characterized by: i) epidermal growth factor receptor EGFR L858R mutation and/or exon 19 deletion; and ii) C797S mutation or wherein the cancer is characterized by epidermal growth factor receptor (EGFR) T790M mutation.

31 . (canceled)

32 . The method of claim 27 , further comprises administering the subject in need thereof an effective amount of afatinib or osimertinib.

33 . (canceled)