Table 5.
Principal Phase Ib–III trials on TKI in KRAS-mutated advanced NSCLC patients.
| Drug | Trial | Phase | Therapy Line * | Treatment Arm | N pts | Main Results | Status |
|---|---|---|---|---|---|---|---|
| Targeting KRAS pathway | |||||||
| Selumetinib (MAPK inhibitor) |
SELECT-1 (NCT01933932) |
III | 2L | Selumetinib + Docetaxel vs. Placebo + Docetaxel |
510 | mPFS = 3.9 vs. 2.8 mo mOS = 8.7 vs. 7.9 mo ORR = 20.1% vs. 13.7% mDOR = 2.9 vs. 4.5 mo |
Closed |
| IND.219 (NCT02337530) |
II | 1L | ARM A: Salumetinib intermittent + Pemetrexed/Platinum |
20 | ORR = 35% mPFS = 7.5 mo |
Closed | |
| ARM B: Salumetinib continuous + Pemetrexed/Platinum |
21 | ORR = 62% mPFS = 6.7 mo |
|||||
| ARM C: Pemetrexed/Platinum |
21 | ORR = 24% mPFS = 4.0 mo |
|||||
| Trametinib (MEK 1-2 inhibitor) |
NCT01362296 | II | ≥2L | Trametinib vs. Docetaxel |
134 | mPFS = 12 vs. 11 weeks mOS = 8 mo vs. NR ORR = 12% vs. 12% |
Closed |
| Momelotinib (JAK1-2 inhibitor) |
NCT02258607 | Ib | ≥2L | Momelotinib + Trametinib |
21 | ORR = NR DCR = 57.1% mPFS = 3.6 mo mOS = 7.4 mo |
Closed |
| Defactinib (FAK inhibitor) |
NCT01951690 | II | ≥2L | Defactinib | 55 | 12wks-PFS = 28% | Closed |
| Targeting KRAS G12C | |||||||
| Sotorasib (AMG510) | CODEBREAK 100 (NCT03600883) |
I/II | ≥2L | Sotorasib | 129 (59 NSCLC) |
ORR = 32.2% DCR = 88.1% mPFS = 6.3 mo |
Ongoing |
| Adagrasib (MRTX849) |
KRYSTAL-1 (NCT03785249) |
I/II | ≥1L | Adagrasib | 110 (79 NSCLC) |
ORR = 45% DCR = 96% |
Ongoing |
| Targeting CDK 4/6 | |||||||
| Abemaciclib (LY2835219) |
JUNIPER (NCT02152631) |
III | ≥2L | Abemaciclib vs Erlotinib |
453 | mOS = 7.4 vs. 7.8 mo mPFS = 3.6 vs. 1.9 mo ORR = 8.9% vs. 2.7% DCR = 54.5% vs. 31.7% |
Ongoing |
1L—first-line; 2L—second-line; vs.—versus; N—number; pts—patients; mPFS—median progression-free survival; mOS—median overall survival; mo—month; ORR—overall response rate; DCR—disease control rate; mDOR—median duration of response; 12wks-PFS—progression-free survival at 12 weeks; NR—not reached. An asterisk (*) indicates the line or lines of treatment for advanced NSCLC in which the investigational agent or regimen was employed in each reported trial.