2

…

3

EGFR KRAS TheraScreen K-RAS

EGFR TK EGFR TheraScreen EGFRRGQ

CCR4 CCR4 T FCM

ALK TK ALK Vysis ALK Break Apart FISH

4

23

0701 10

5

6

0701 10

Q&A)

7

8

11.11.21.31.4

22.1

2.1.12.1.22.1.3

2.2

33.13.2

3.2.13.2.2

3.3 4

9

1.1

1.2

1.3

1.4

10

1.

1.1

QA25 7 1

11

1.2

•

PMDA

12

1.3

7 1

13

1.4

•

•

14

2.1

2.1.1

2.1.2

2.1.3

2.2

15

2

2.1.1

•

•

16

2.1.1

•

•

17

•

18

Panitumumab< EGFR >

19

EGFREGFR

Crizotinib <ALK TK > FDA

FDA Letter1789-11 To assess the adequacy of the current cut-off, conduct a clinical trial to explore response to crizotinib in ALK-negative patients based on current assay cut-off. This should be compared to historic controls and to the response in ALK-positive patients. Additional biomarkers should be assessed in ALK-negative patients.

2012 FDA

ALK Response rate NALK FISH positive 50%, 61% 136, 119ALK FISH negative 26% 23

20

ALK

21

ALK

22

• Off-target effect

•

•• Intra-tumor heterogeneity

23

24

EGFR

EGFR KRAS

KRAS EGFR

2.1.2

•

25

2.1.2

••

26

2.1.2

•

•

•

•

• 4

PMDA

27

•

•

28

2.1.3

2.2

•

29

3

3.1

3.2

3.2.1

3.2.2

3.3

30

3.1

•

31

3.2

32

•

•

•

3.2

33

•

3.3

•

34