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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