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Table 3 Clinical trials investigated in non-small cell lung cancer targeting KRAS pathway

From: KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target

Target

Drug/drug combination

Date

Phase

Patients

Line

KRAS status

Primary endpoint

RR, %

PFS (months)

OS (months)

NCT

Farnesyl transferase

Tipifarnib [91]

2003

II

44

1

Unknown

ORR

0

2.7

7.7

NCT00005989

Farnesyl transferase

CI-1040 [102]

2004

I

67

≥1

Unknown

ORR

0

4.4

NA

NCT00033384

C-Raf

PD-0325901 [105]

2010

II

34

≥1

Unknown

ORR

0

1.8

7.8

NCT00174369

C-Raf

Selumetinib/pemetrexed [107]

2010

II

84

2 or 3

Unknown

Disease progression event

5 vs 4

2.2 vs 3

NA

NCT00372788

Mek

Salirasib [92]

2011

II

33

All lines

Mut

Rate of nonprogression at 10 weeks

0

TTP: 2 (1st line), 1 (2nd line)

Not reached (1st line), 15 (2nd line)

NCT00531401

Mek

Tivantinib + erlotinib/placebo + erlotinib [120]

2011

II

167

> 1

Mut, wt, unknown

PFS

10 vs 7

3.8 vs 2.3

8.5 vs 6.9

NCT00777309

Mek

RO5126766 [103]

2012

I

52

All lines

Unknown

Safety

6.6

NA

NA

NCT00777309

Mek

Cobimetinib + pictilisib [129]

2012

Ib

78

NS

Unknown

Safety

14

NA

NA

NCT00996892

Mek

Ridaforolimus [126]

2012

II

79

> 1

Mut

PFS

1

4

18

NCT00818675

Mek

Tivantinib + erlotinib/placebo + erlotinib [121]

2012

III

1048

2 or 3

Mut, wt, unknown

OS

NS

3.6 vs 1.9

8.5 vs 7.8

NCT01244191

Mek

RO5126766 [104]

2013

I

12

> 1

Unknown

Safety

0

NA

NA

–

Mek

Trametinib + docetaxel [113]

2013

I/Ib

46

> 1

Mut, wt

Safety

17 (KRAS-mut: 17)

NA

NA

NCT01192165

Proteasome

Trametinib + pemetrexed [116]

2013

I/Ib

42

> 1

Mut, wt

Safety

14.3 (KRAS-mut: 15)

NA

NA

NCT01192165

Mek

Trametinib + gemcitabine (2014)

2013

Ib

31

All lines

Unknown

Safety

30

NA

NA

NCT01428427

Met

Pimasertib + voxtalisib [130]

2013

Ib

53

NS

NS

Safety

7

NA

NA

NCT01390818

Mek

Sorafenib [98]

2013

II

59

> 1

Mut

DCR at 6 weeks

10.5

2.3

5.3

NCT00064350

Mek

Selumetinib + docetaxel/placebo + docetaxel [109]

2013

II

87

2

Mut

OS

37 vs 0

5.3 vs 2.1

9.4 vs 5.2

NCT00890825

Met

Onartuzumab + erlotinib/placebo + erlotinib [122]

2013

II

137

≥2

Mut, wt, unknown

PFS

5.8 vs 4.4

2.2 vs 2.6

8.9 vs 7.4 (KRAS-mut: 10.4 vs 7.7)

NCT00854308

Met

Ganetespib [137]

2013

II

99

> 1

Mut, wt

PFS at 16 weeks

KRAS-mut: 0

KRAS-mut: 1.9

KRAS-mut: 11

NCT01031225

mTOR

Copanlisib + refametinib [131]

2014

Ib

49

NS

Mut, wt, unknown

Safety

2.2

NA

NA

NCT01392521

Mek, PI3k

Alpelisib + binimetinib [132]

2014

Ib

58

NS

Mut

Safety

8.6

NA

NA

NCT01449058

Mek, PI3k

Trametinib/docetaxel [113]

2015

II

129

2

Mut

PFS

12 vs 12

3 vs 2.75

2 vs NR

NCT01362296

Mek, PI3k

Bortezomib [119]

2015

II

16

≥2

Mut

ORR

6.6

1

13

NCT01833143

Fak

Defactinib [134]

2015

II

55

≥2

Mut

PFS at 12 weeks

1.8

NA

NA

NCT01951690

Hsp90

Ganetespib + docetaxel/Docetaxel [138]

2015

II

385

2

Mut, wt

PFS

NA

KRAS-mut: 3.9 vs 3.0

KRAS-mut: 7.6 vs 6.4

NCT01348126

Mek, PI3k, mTOR

Sorafenib/placebo [99]

2015

III

706

3 or 4

Mut, wt

OS

4.9 vs 0.9 (KRAS-mut: 2.9 vs 0)

2.8 vs 1.4 (KRAS-mut: 2.6 vs 1.7)

8.2 vs 8.3 (KRAS-mut: 6.4 vs 5.1)

NCT00863746

Mek

Selumentinib + erlotinib/placebo + erlotinib [112]

2016

II

89

2 or 3

Mut, wt

PFS, ORR

10 vs 0 (mut)

2.3 vs 4 (mut)

21.8 vs 10.5 (mut)

NCT01229150

Host immunity

Paclitaxel + carboplatin + reolysin [139]

2016

II

37

≥1

Mut, wt

ORR

31

12

4

NCT 00861627

Hsp90

Selumetinib + docetaxel/placebo + docetaxel [111]

2017

III

505

2

Mut

PFS

20.1 vs 13.7

3.9 vs 2.8

8.7 vs 7.9

NCT01933932