Review Article
Colorectal Cancer: From Genetic Landscape to Targeted Therapy
Table 3
TKIs targeting EGFR pathway under clinical investigation.
| | Drugs | Target | Setting | Treatment | Phase | Identifiers |
| | Erlotinib | EGFR | 2nd line k-RAS WT mCRC | Erlotinib + panitumumab ± irinotecan | II | NCT00940316 | | Neratinib | EGFR/HER2 | KRAS/NRAS/BRAF/PIK3CA wild-type mCRC | Neratinib + Trastuzumb vs. Neratinib + Cetuximab | II | NCT03457896 | | Sapitinib (AZD8931) | EGFR/HER2/3 | Recurrent or metastatic CRC | AZD8931 + FOLFIRI | II | NCT01862003 | | Tucatinib | HER2 | HER2 positive CRC | Tucatinib + trastuzumab | II | NCT03043313 | | Lapatinib (GSK572016) | EGFR/HER2/erk-1/2 | 2nd line advanced or mCRC | Lapatinib + capecitabine | II | NCT00574171 | | Vemurafenib | BRAF (V600E) | BRAF V600E mutation and advanced CRC | FOLFIRI + Cetuximab + Vemurafenib | II | NCT03727763 | | Dabrafenib | BRAF (V600E) | BRAF V600E mutation mCRC | Dabrafenib + trametinib + spartalizumab | II | NCT03668431 | | Encorafenib (LGX-818) | BRAF (V600E) | MSS/BRAF V600E mCRC | Encorafenib + Cetuximab + nivolumab | I/II | NCT04017650 | | BMS-908662 | BRAF | Mutant BRAF mCRC | BMS-908662 + cetuximab | I/II | NCT01086267 | | Binimetinib (MEK162) | MEK1/2 | RAS positive mCRC | Binimetinib + mFOLFIRI | I | NCT02613650 | | Cobimetinib | MEK1 | Locally advanced and metastatic CRC | Cobimetinib + Atezolizumab vs. Regorafenib | III | NCT02788279 | | Trametinib | MEK1/2 | RAS/RAF mutant and TP53 WT mCRC | Trametinib + HDM201 | I | NCT03714958 | | Selumetinib (AZD6244) | MEK1/2 | 2nd line k-RAS BRAF mCRC | Selumetinib + irinotecan | II | NCT01116271 | | Alpelisib (BYL719) | PI3K | BRAF mutant mCRC | Alpelisib + Cetuximab vs. BYL719 + Cetuximab + LGX818 | I/II | NCT01719380 | | Buparlisib (BKM120) | PI3K | Wild-type RAS advanced or metastatic CRC | Panitumumab + BKM120 | I/II | NCT01591421 | | Gedatolisib (PF05212384) | PI3K/mTOR | mCRC | Gedatolisib + FOLFIRI vs. FOLFIRI + Bevacizumab | I/II | NCT01937715 | | Nab-rapamycin (ABI-009) | mTOR | 1st line advanced or metastatic CRC | ABI-009 + FOLFOX + bevacizumab | I/II | NCT03439462 | | Everolimus (RAD001) | mTOR | 2nd line mCRC | Irinotecan + Cetuximab ± Everolimus | I/II | NCT00522665 | | ONC201 | AKT/ERK | MSS mCRC | ONC201 + Nivolumab | I/II | NCT03791398 | | MK2206 | AKT | WT k-RAS/mutated PIK3CA mCRC | MK2206 | II | NCT01186705 | | TTI-101 | STAT3 | Advanced CRC | TTI-101 | I | NCT03195699 | | Ruxolitinib | JAK/STAT3 | RAS mutant advanced CRC and pancreatic cancer | Ruxolitinib + trametinib | I | NCT04303403 |
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mCRC: metastatic colorectal cancer; FOLFIRI: irinotecan in combination with 5-fluorouracil and folinic acid; MSS: microsatellite stability; FOLFOX: leucovorin calcium, fluorouracil, and oxaliplatin; KRAS: Kirsten rat sarcoma viral oncogene; WT Kras: wild-type Kras; HER: human epidermal growth factor receptor; EGFR: epidermal growth factor receptor; BRAF: v-raf murine sarcoma viral oncogene homolog B1; PIK3: phosphatidylinositol 3-kinase; mTOR: mammalian target of rapamycin. JAK: Janus kinase; STAT3: signal transducer and activator of transcription 3.
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