29.11 - city.kita.tokyo.jp · keynote-087 210 10 3 200 mg 3 1 2 3 iwg criteria 2007 cr pr 1 20% 1...

1130

29 11 30

2016 28

20mg 100mg

29 140214

29.11.30

1 KEYNOTE-024 200 mg

Q3W 154

151

PFS

95%CI

10. 3 6. 7, NE

6. 0 4. 2, 6. 2

95%CIP

0. 50 0. 37,

0. 68 0. 001

OS

95%CI

NE NE, NE

NE 9. 4, NE

95%CIP

0. 60 0. 41,

0. 89 0. 005

CI NE *1 RECIST1. 1 *2

Cox

1

*3*4 2016 5 9

2 KEYNOTE-010

2 mg/ kg Q3W

344

10 mg/ kg Q3W

346

343OS

95%CI

10. 4 9. 4,

11. 9

12. 7 10. 0,

17. 3

8. 5 7. 5,

9. 8

95%CI

P

0. 71 0. 58,

0. 88 0. 001

0. 61 0. 49,

0. 75 0. 001

CI *1 Cox*2

2

3 5%

SOC: System Organ Cl ass

PT: Preferred Term

5%

SOC PT

MedDRA ver. 19. 0 MedDRA ver. 19. 0

4 5%


PT: Preferred Term MedDRA ver. 18. 0

5%

SOC PT

MedDRA ver. 18. 0

10 -1 1 5

(1)

29 1 434(2) 29 1 85

(3)

- 1 1 5

(1)

28 10 1 427

(2) 28 1 84

( 4)

28 7 12540

(5) 28 7 1

1290

(3)

( 4)

27 71 2538

(5) 27 7 1

1284 11 -3

i nfusi on reacti on

10 -3


RECIST

1. 1 CRPR 24% 95% 12

4110%

RECIST1. 1 CR

PR 24% 95% 1241

1 KEYNOTE-002 2

mg/ kgQ3W 180

10 mg/ kgQ3W

181 179

OS

95%CI

13. 4 11. 0,

16. 4

14. 7 11. 3,

19. 5

11. 0 8. 9,

13. 8

95%CIP

0. 86 0. 67,

1. 10 0. 1173

0. 74 0. 57,

0. 96 0. 0106

PFS 2. 9 2. 9 2. 7

95%CI

2. 8, 3. 8

2. 8, 4. 7

2. 5, 2. 8

95%CIP

0. 57 0. 45,

0. 73

0. 0001

0. 50 0. 39,

0. 64

0. 0001

CI *1 RECIST 1. 1

*2 Cox*3

2 KEYNOTE-006 10

mg/ kg Q3W 277

10 mg/ kg Q2W 279

278

OS

95%CI

NE NE,

NE

NE NE,

NE

NE 13,

NE

95%CIP

0. 69 0. 52,

0. 90 0. 00358

0. 63 0. 47,

0. 83 0. 00052

PFS

4. 1 2. 9,

5. 5 3. 4,

2. 8 2. 8,

95%CI 6. 9 6. 9 2. 9

95%CIP

0. 58 0. 47,

0. 72

0. 00001

0. 58 0. 46,

0. 72

0. 00001

CI NE *12015 3 3 *2

Cox*3 *4 RECIST

1. 1*5

2014 9 3 3 5%

SOC: System Organ Cl ass PT: Preferred Term

MedDRA ver. 18. 0

5%

SOC PT

MedDRA ver. 18. 0

4 5%



5%

SOC PT

MedDRA ver. 18. 0

10 5 5%



5%

SOC PT

MedDRA ver. 18. 0 10

11 -1 1 5

(1)

10 -1 1 5

(1)

29 1 434(2) 29 1 85

(3)

( 4)

28 7 12540

(5) 28 7 1

1290

28 10 1 427

(2) 28 1 84

(3)

( 4)

27 71 2538

(5) 27 7 1

1284 12 -3


11 -3


20 mg 100 mg

1

1. P2 2. P3 3. P4 4. P6 5. P8 6. P9

2

1.

2016 28

20 mg 100 mg

1

200 mg 3 30 MSD

3

2 20 mg 100 mg

PD-1 programmed cell death-1PD-L1 PD-L2 IgG4 PD-1 T

PD-1 TPD-1

PD-L1T

PD-L1

PD-L1 PD-1 PD-L1

PD-1 PD-L1 PD-L2

T

4

3

KEYNOTE-087

210 103 200 mg 3

1

2

3

IWG criteria 2007 CR PR

120%

1 KEYNOTE-087

1

69 2

81 3

60

%

CR 15 21.7 18 22.2 13 21.7 PR 35 50.7 35 43.2 27 45.0

SD 13 18.8 9 11.1 13 21.7 PD 3 4.3 17 21.0 7 11.7

3 4.3 2 2.5 0

CR PR % 95%

72.5 60.4, 82.5

65.4 54.0, 75.7

66.7 53.3, 78.3

5

KEYNOTE-087

202/210 96.2% 144/210 68.6%5% 2

2 5%

SOC: System Organ ClassPT: Preferred Term

MedDRA/J ver.19.0

%

210 Grade Grades 3

144 (68.6) 23 (11.0) 11 (5.2) 5 (2.4) 26 (12.4) 1 (0.5) 15 (7.1) 2 (1.0) 12 (5.7) 0 (0.0)

19 (9.0) 1 (0.5) 22 (10.5) 1 (0.5) 13 (6.2) 0 (0.0) 12 (5.7) 1 (0.5) 16 (7.6) 0 (0.0)

6 2.9% 3 1.4%1 0.5% 8 3.8%

29 13.8% 2 1.0% Infusion reaction 17 8.1%2 1.0% 1 0.5%

1

6

4

-1 1 5

(1) 29 4 1 434

(2) 29 6 1 85 (3)

(4) 1 2

28 7 1 2540 (5) 28 7

1 1290

-2

2 52

2 43

7

-1

24CT

-2

-3

1

infusion reaction

8

5

ECOG Performance Status 3-4 1

1 ECOG Performance Status PS

Score 0

1

2 50%3 50% 4

9

6

X

CT

infusion reaction infusion reaction

TSH T3 T4

AST ALT -GTP Al-P

1 1

1

12

20 mg 100 mg

1

1. P2 2. P3 3. P4 4. P10 5. P12 6. P14

2

1.

2016 28

20 mg 100 mg

PD-L1 1

200mg 3 30 MSD

3

2 20 mg 100 mg


PD-1 TPD-1

PD-L1T

PD-L1

PD-L1 PD-1 PD-L1

PD-1 PD-L1 PD-L2

T

4

3 PD-L1

KEYNOTE-024

EGFR ALK PD-L1 PD-L1TPS 50% *

305 40 200 mg 3SOC

PFS OSPFS OS

* PD-L1 IHC 22C3 pharmDx

1 KEYNOTE-024

200 mg Q3W 154

151

PFS*1

95%CI

10.3 6.7, NE

6.0 4.2, 6.2

*2 95%CI P *3

0.50 0.37, 0.68

0.001

OS*4

95%CI

NE NE, NE

NE 9.4, NE

*4 95%CI P *3

0.60 0.41, 0.89

0.005

CI NE *1 RECIST 1.1 *2Cox *3

*4 2016 5 9

5

PFS Kaplan-Meier PD-L1 50%

OS Kaplan-Meier PD-L1 50%

6

/ KEYNOTE-010 *1 PD-L1 TPS 1% *2

1,033 91 2 mg/kg 310 mg/kg 3

DOC

OS PFS DOC OS *1 EGFR ALK

EGFR ALK

*2 PD-L1 IHC 22C3 pharmDx

2 KEYNOTE-010 2 mg/kg

Q3W 344

10 mg/kg Q3W

346

343 OS

95%CI 10.4

9.4, 11.9 12.7

10.0, 17.3 8.5

7.5, 9.8 *1

95%CI P *2

0.71 0.58, 0.88

0.001

0.61 0.49, 0.75

0.001

CI *1 Cox *2

OS Kaplan-Meier PD-L1 1%

7

KEYNOTE-024

148/154 96.1% SOC 145/150 96.7%113/154 73.4%

135/150 90.0% 5%

3 5% SOC: System

Organ Class PT: Preferred Term

MedDRA ver.19.0

%

154 SOC 150

Grade Grade 3 Grade Grade 3 113 (73.4) 41 (26.6) 135 (90.0) 80 (53.3)

8 (5.2) 3 (1.9) 66 (44.0) 29 (19.3)

1 (0.6) 0 8 (5.3) 2 (1.3) 1 (0.6) 0 34 (22.7) 20 (13.3) 0 0 17 (11.3) 8 (5.3)

11 (7.1) 0 0 0 12 (7.8) 0 1 (0.7) 0

6 (3.9) 0 17 (11.3) 0 22 (14.3) 6 (3.9) 20 (13.3) 2 (1.3) 15 (9.7) 0 65 (43.3) 3 (2.0)

4 (2.6) 0 18 (12.0) 2 (1.3) 4 (2.6) 1 (0.6) 30 (20.0) 1 (0.7)

5 (3.2) 1 (0.6) 11 (7.3) 2 (1.3)

16 (10.4) 2 (1.3) 43 (28.7) 5 (3.3) 1 (0.6) 0 9 (6.0) 0

16 (10.4) 0 8 (5.3) 0

10 (6.5) 0 7 (4.7) 0

8 (5.2) 2 (1.3) 5 (3.3) 0

3 (1.9) 0 15 (10.0) 1 (0.7) 0 0 20 (13.3) 6 (4.0) 0 0 18 (12.0) 9 (6.0) 1 (0.6) 0 16 (10.7) 3 (2.0)

14 (9.1) 0 39 (26.0) 4 (2.7)

1 (0.6) 0 9 (6.0) 0

13 (8.4) 0 4 (2.7) 0 1 (0.6) 0 15 (10.0) 0

2 (1.3) 0 9 (6.0) 1 (0.7)

8 (5.2) 4 (2.6) 1 (0.7) 1 (0.7)

0 0 12 (8.0) 0 8 (5.2) 0 1 (0.7) 0 12 (7.8) 0 3 (2.0) 0

11 (7.1) 1 (0.6) 3 (2.0) 0

8

9 5.8% 8 5.2%2 1.3% 22 14.3%

21 13.6% 1 0.6% 1 10.6% 1 0.6% 1 0.6%

1 0.6% infusion reaction 5 3.2%

/ KEYNOTE-010 2 mg/kg Q3W 331/339 97.6% 10 mg/kg Q3W 330/343 96.2%

DOC 297/309 96.1%215/339 63.4% 226/343 65.9% 251/309 81.2%

5%

9

4 5%

SOC: System Organ Class

PT: Preferred TermMedDRA ver.18.0

%2 mg/kg Q3W

339 10 mg/kg Q3W

343 DOC 309

Grade Grade 3 Grade Grade 3 Grade Grade 3 215 (63.4) 43 (12.7) 226 (65.9) 55 (16.0) 251 (81.2) 109 (35.3)

10 (2.9) 3 (0.9) 14 (4.1) 1 (0.3) 40 (12.9) 5 (1.6)

1 (0.3) 0 1 (0.3) 0 44 (14.2) 38 (12.3)

25 (7.4) 0 23 (6.7) 0 1 (0.3) 0

24 (7.1) 2 (0.6) 22 (6.4) 0 56 (18.1) 7 (2.3) 37 (10.9) 1 (0.3) 31 (9.0) 2 (0.6) 45 (14.6) 1 (0.3)

13 (3.8) 0 7 (2.0) 1 (0.3) 43 (13.9) 3 (1.0) 12 (3.5) 0 13 (3.8) 1 (0.3) 24 (7.8) 2 (0.6)

20 (5.9) 1 (0.3) 19 (5.5) 2 (0.6) 35 (11.3) 6 (1.9) 46 (13.6) 4 (1.2) 49 (14.3) 6 (1.7) 76 (24.6) 11 (3.6)

5 (1.5) 0 4 (1.2) 0 21 (6.8) 0 10 (2.9) 1 (0.3) 14 (4.1) 0 17 (5.5) 1 (0.3)

0 0 2 (0.6) 0 24 (7.8) 19 (6.1)0 0 3 (0.9) 0 16 (5.2) 10 (3.2)

46 (13.6) 3 (0.9) 33 (9.6) 1 (0.3) 49 (15.9) 3 (1.0)

13 (3.8) 0 19 (5.5) 2 (0.6) 18 (5.8) 0 9 (2.7) 0 10 (2.9) 0 29 (9.4) 0

4 (1.2) 0 7 (2.0) 0 16 (5.2) 0

2 (0.6) 0 3 (0.9) 0 28 (9.1) 1 (0.3) 3 (0.9) 0 3 (0.9) 0 17 (5.5) 0

3 (0.9) 0 2 (0.6) 0 101 (32.7) 2 (0.6)

25 (7.4) 0 32 (9.3) 0 5 (1.6) 1 (0.3) 29 (8.6) 1 (0.3) 44 (12.8) 1 (0.3) 14 (4.5) 0

2 mg/kg Q3W 10 mg/kg Q3W 15 4.4%

14 4.1% 5 1.5% 2 0.6%1 0.3% 1 0.3%

2 0.6% 3 0.9%23 6.8% 22 6.4% 32 9.4% 35 10.2%

1 0.3% 1 0.3% 2 0.6% 10.3% 1 1 0.3% 2 0.6%

4 1.2% 0 1 0.3% 01 0.3% 0 infusion reaction 2 0.6% 6 1.7%

10

4

-1 1 5

(1) 29 4 1 434

(2) 29 6 1 85 (3)

(4) 1 2

28 7 1 2540 (5) 28 7

1 1290

-2

2 52

2 43

11

-1

24CT

-2

-3

1

infusion reaction

12

5


EGFR ALK PD-L1

TPS 50% PD-L1 TPS 1%

EGFR ALKEGFR ALK

TPS

PD-L1 IHC 22C3 pharmDx


Score 0

1

2 50%3 50% 4

13

ECOG Performance Status 0 11 75 ECOG Performance Status 2 1 3

3

14

6

X

CT


TSH T3 T4

AST ALT -GTP Al-P

1 1

1

9 13

20 mg 100 mg

1

1. P2 2. P3 3. P4 4. P11 5. P13 6. P14

2

1

2016 28

20 mg 100 mg

1

2mg/kg 3 30MSD

3

2 20 mg 100 mg


PD-1 TPD-1

PD-L1T

PD-L1

PD-L1 PD-1 PD-L1

PD-1 PD-L1 PD-L2

T

4

3

b KEYNOTE-041

2 4237 2 mg/kg 3 Q3W

RECIST 1.1 CRPR 24% 95% 12 41

10%

KEYNOTE-002 2

mg/kg Q3W 10 mg/kg Q3W

ICC

OS PFSPFS


Q3W 180

10 mg/kg Q3W

181

179 OS

95%CI 13.4

11.0, 16.4 14.7

11.3, 19.5 11.0

8.9, 13.8 *2

95%CI P *3

0.86 0.67, 1.10

0.1173

0.74 0.57, 0.96

0.0106

PFS*1 95%CI

2.9 2.8, 3.8

2.9 2.8, 4.7

2.7 2.5, 2.8

*2 95%CI P *3

0.57 0.45, 0.73

0.0001

0.50 0.39, 0.64

0.0001

CI *1 RECIST 1.1*2 Cox *3

5

OS Kaplan-Meier

PFS Kaplan-Meier

6

KEYNOTE-006 1

10 mg/kg Q3W10 mg/kg 2 Q2W

OS PFSOS PFS


Q3W 277

10 mg/kg Q2W

279

278 OS*1

95%CI NE

NE, NE NE

NE, NE NE

13, NE *2

95%CI P *3

0.69 0.52, 0.90

0.00358

0.63 0.47, 0.83

0.00052

PFS*4

5

95%CI

4.1 2.9, 6.9

5.5 3.4, 6.9

2.8 2.8, 2.9

*2 95%CI P *3

0.58 0.47, 0.72

0.00001

0.58 0.46, 0.72

0.00001

CI NE *1 2015 3 3 *2

Cox *3 *4 RECIST

1.1 *5

2014 9 3

7

OS Kaplan-Meier

PFS Kaplan-Meier

8

b KEYNOTE-041

41/42 97.6%34/42 81.0% 5%

3 5%

SOC: System Organ Class PT: Preferred Term

MedDRA ver.18.0

%

2 mg/kg Q3W 42

Grades Grades 3 34 (81.0) 8 (19.0)

4 (9.5) 0 (0.0) 3 (7.1) 0 (0.0)

5 (11.9) 0 (0.0) 3 (7.1) 0 (0.0) 3 (7.1) 0 (0.0) 6 (14.3) 0 (0.0) 6 (14.3) 0 (0.0) 3 (7.1) 0 (0.0)

1 2.4% 2 4.8% 3

7.1% 2 4.8% 6 14.3% infusion reaction 1 2.4% 1 2.4%

1

KEYNOTE-002 2 mg/kg Q3W 172/178 96.6% 10 mg/kg Q3W 178/179 99.4%

ICC 167/171 97.7%121/178 68.0% 133/179 74.3% 138/171 80.7%

5%

9

4 5%

SOC: System Organ ClassPT: Preferred Term

MedDRA ver.18.0

% 2 mg/kg Q3W

178 10 mg/kg Q3W

179 ICC 171

Grades Grades 3 Grades Grades 3 Grades Grades 3 121 (68.0) 20 (11.2) 133 (74.3) 25 (14.0) 138 (80.7) 45 (26.3) 5 (2.8) 1 (0.6) 7 (3.9) 0 (0.0) 35 (20.5) 9 (5.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 14 (8.2) 6 (3.5) 1 (0.6) 0 (0.0) 1 (0.6) 0 (0.0) 14 (8.2) 6 (3.5) 2 (1.1) 0 (0.0) 1 (0.6) 1 (0.6) 16 (9.4) 4 (2.3) 9 (5.1) 0 (0.0) 13 (7.3) 0 (0.0) 0 (0.0) 0 (0.0) 5 (2.8) 0 (0.0) 9 (5.0) 0 (0.0) 14 (8.2) 0 (0.0) 15 (8.4) 0 (0.0) 19 (10.6) 2 (1.1) 14 (8.2) 3 (1.8) 8 (4.5) 0 (0.0) 16 (8.9) 1 (0.6) 56 (32.7) 4 (2.3) 2 (1.1) 1 (0.6) 10 (5.6) 1 (0.6) 26 (15.2) 4 (2.3)

6 (3.4) 1 (0.6) 8 (4.5) 1 (0.6) 10 (5.8) 1 (0.6) 40 (22.5) 2 (1.1) 52 (29.1) 1 (0.6) 62 (36.3) 8 (4.7) 6 (3.4) 0 (0.0) 11 (6.1) 0 (0.0) 8 (4.7) 1 (0.6) 0 (0.0) 0 (0.0) 1 (0.6) 0 (0.0) 13 (7.6) 5 (2.9) 8 (4.5) 0 (0.0) 17 (9.5) 2 (1.1) 26 (15.2) 0 (0.0) 13 (7.3) 1 (0.6) 12 (6.7) 1 (0.6) 9 (5.3) 1 (0.6) 9 (5.1) 2 (1.1) 7 (3.9) 0 (0.0) 10 (5.8) 1 (0.6) 2 (1.1) 0 (0.0) 0 (0.0) 0 (0.0) 14 (8.2) 2 (1.2) 1 (0.6) 0 (0.0) 2 (1.1) 0 (0.0) 11 (6.4) 0 (0.0) 5 (2.8) 0 (0.0) 1 (0.6) 0 (0.0) 35 (20.5) 1 (0.6) 9 (5.1) 0 (0.0) 9 (5.0) 0 (0.0) 2 (1.2) 0 (0.0) 37 (20.8) 0 (0.0) 42 (23.5) 0 (0.0) 6 (3.5) 0 (0.0) 21 (11.8) 0 (0.0) 18 (10.1) 0 (0.0) 8 (4.7) 0 (0.0) 5 (2.8) 1 (0.6) 10 (5.6) 1 (0.6) 0 (0.0) 0 (0.0) 10 (5.6) 0 (0.0) 9 (5.0) 0 (0.0) 2 (1.2) 0 (0.0)

2 mg/kg Q3W 10 mg/kg Q3W 1 0.6%4 2.2% 1 0.6% 6 3.4%

2 1.1% 0 13 7.3% 15 8.4%1 0.6% 1 0.6% 1

0.6% 3 1.7% 14 7.9% 15 8.4% infusion reaction 2 1.1% 3 1.7%

1 0.6% 1 0.6% 1 0.6% 00 1 0.6% 0 1 0.6%

0 2 1.1% 1

10

KEYNOTE-006 10 mg/kg Q3W 264/277 95.3% 10 mg/kg Q2W 275/278 98.9%

IPI 239/256 93.4%202/277 72.9% 221/278 79.5% 187/256 73.0%

5%

5 5%

SOC: System Organ Class PT: Preferred Term

MedDRA ver.18.0

% 10 mg/kg Q3W

277 10 mg/kg Q2W

278 IPI 256

Grades Grades 3 Grades Grades3 Grades Grades 3 202 (72.9) 28 (10.1) 221 (79.5) 37 (13.3) 187 (73.0) 51 (19.9)

7 (2.5) 0 (0.0) 17 (6.1) 0 (0.0) 6 (2.3) 1 (0.4) 21 (7.6) 0 (0.0) 25 (9.0) 1 (0.4) 2 (0.8) 0 (0.0) 5 (1.8) 0 (0.0) 10 (3.6) 0 (0.0) 15 (5.9) 0 (0.0) 8 (2.9) 5 (1.8) 4 (1.4) 4 (1.4) 19 (7.4) 16 (6.3) 40 (14.4) 3 (1.1) 47 (16.9) 7 (2.5) 58 (22.7) 8 (3.1) 11 (4.0) 0 (0.0) 20 (7.2) 0 (0.0) 1 (0.4) 0 (0.0) 31 (11.2) 1 (0.4) 28 (10.1) 0 (0.0) 22 (8.6) 1 (0.4) 5 (1.8) 0 (0.0) 10 (3.6) 1 (0.4) 14 (5.5) 0 (0.0) 31 (11.2) 0 (0.0) 32 (11.5) 1 (0.4) 16 (6.3) 2 (0.8) 53 (19.1) 1 (0.4) 58 (20.9) 0 (0.0) 39 (15.2) 3 (1.2) 6 (2.2) 1 (0.4) 14 (5.0) 0 (0.0) 6 (2.3) 2 (0.8) 18 (6.5) 0 (0.0) 17 (6.1) 0 (0.0) 20 (7.8) 0 (0.0)

32 (11.6) 1 (0.4) 26 (9.4) 0 (0.0) 13 (5.1) 2 (0.8) 6 (2.2) 0 (0.0) 19 (6.8) 1 (0.4) 5 (2.0) 1 (0.4)

39 (14.1) 0 (0.0) 40 (14.4) 0 (0.0) 65 (25.4) 1 (0.4) 37 (13.4) 0 (0.0) 41 (14.7) 0 (0.0) 37 (14.5) 2 (0.8) 31 (11.2) 0 (0.0) 25 (9.0) 0 (0.0) 4 (1.6) 0 (0.0)

10 mg/kg Q3W 10 mg/kg Q2W 4 1.4%1 0.4% 10 3.6% 13 4.7%

2 0.7% 0 14 5.1% 238.3% 2 0.7% 1 0.4%

1 0.4% 1 0.4% 28 10.1% 3311.9% 1 0.4% 2 0.7% infusion reaction 7 2.5%5 1.8% 1 1 0.4% 0

0 1 0.4% 1 0.4% 1 0.4%1 0.4% 0 0 1 0.4%

3 1.1% 1 0.4%

11

4

-1 1 5

(1) 29 4 1

434 (2) 29 6 1 85 (3)

(4) 1 2

28 7 1 2540 (5) 28 7

1 1290

-2

2 52

2 5

12

-1

24CT

-2

-3

1

infusion reaction

13

5


BRAF BRAF


Score 0

1

2 50%

3 50% 4

14

6

X

CT


TSH T3 T4

AST ALT -GTP Al-P

1 1

1

3 16

29.11 - city.kita.tokyo.jp · keynote-087 210 10 3 200 mg 3 1 2 3 iwg criteria 2007 cr pr 1 20% 1...

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