Table 1.
Selected molecular subtypes of colorectal cancer and associated clinical trials utilising targeted agents
| Tumour subtype | Investigative strategies | Agents | Phase of trial | Clinicaltrials.gov identifier |
|---|---|---|---|---|
| Mismatch repair deficient/microsatellite instable | PARP inhibition | Olaparib | II | NCT00912743 |
| Immune checkpoint inhibition (PD-L1) | Durvalumab (MEDI4736) | II | NCT02227667 | |
| Immune checkpoint inhibition (PD-L1) | Atezolizumab (MPDL3280A) | II | NCT02291289 | |
| Immune checkpoint inhibition (PD-1) | Nivolumab ± Ipilimumab | I/II | NCT02060188 | |
| Immune checkpoint inhibition (PD-1) | Pembrolizumab (MK-3475) | II | NCT02460198 | |
| ± standard chemotherapy | III | NCT02563002 | ||
| RAS mutation | Pan-RAF inhibition | BMS-908662 ± Cetuximab | I/II | NCT01086267 |
| AKT and MEK inhibition | MK-2206 and AZD6244 (Selumetinib) | II | NCT01333475 | |
| HDAC inhibition | 4SC-201 (Resminostat) + FOLFIRI | II | NCT01277406 | |
| ERK inhibition | CC-90003 | I | NCT02313012 | |
| NOTCH inhibition | RO4929097 + Cetuximab | I | NCT01198535 | |
| MEK and MET inhibition | PD-0325901 + Crizotinib | I | NCT02510001 | |
| Multikinase inhibition | Regorafenib | II | NCT02175654 | |
| MEK and BCL2 inhibition | Trametinib and Navitoclax (ABT-263) | I/II | NCT02079740 | |
| PI3K and MEK inhibition | BKM120 + MEK162 | I | NCT01363232 | |
| Resistant to EGFR inhibition | RAF inhibition | BMS-908662 ± Cetuximab | I/II | NCT01086267 |
| NOTCH inhibition | RO4929097 + Cetuximab | I | NCT01198535 | |
| BRAF mutation | PI3K and MEK inhibition | BKM120 + MEK162 | I | NCT01363232 |
| BEZ235 + MEK162 | I | NCT01337765 | ||
| BRAF, MEK and EGFR inhibition | Trametanib, Dabrafenib + Panitumumab | II | NCT01750918 | |
| RAF inhibition | BMS-908662 ± cetuximab | I/II | NCT01086267 | |
| BRAF and EGFR inhibition | Irinotecan, Cetuximab + Vemurafenib | II | NCT02164916 | |
| BRAF, PI3K and EGFR inhibition | LGX818, BYL719, and Cetuximab | I/II | NCT01719380 | |
| BRAF, WNT and EGFR inhibition | LGX818, WNT974 and Cetuximab | I/II | NCT02278133 | |
| ERK inhibition | BVD-523 | I | NCT02313012 | |
| ERK inhibition | CC-90003 | I | NCT02313012 | |
| PI3K mutation/PTEN depletion | MEK and PI3K/mTOR inhibition | Pimasertib + SAR245409 | I | NCT01390818 |
| AKT and MEK inhibition | MK-2206 and AZD6244 (selumetinib) | II | NCT01333475 | |
| HER2 amplification | HER2 dual inhibition | Trastuzumab + Lapatinib | II | EudraCT Number: 2012-002128-33 |
| Trastuzumab + Pertuzumab | II | |||
| MET amplification | MEK and MET inhibition | PD-0325901 + Crizotinib | I | NCT02510001 |