Table 1.
List of therapeutic approaches targeting KRAS-RAF-MEK in clinical trials and FDA-approved
| Therapy | Direct target | Cancer type | Trial phase and combinations | Clinical trial ID# | Sponsor |
|---|---|---|---|---|---|
| AMG 510 (sotorasib) | KRAS G12C |
KRASG12C mutant NSCLC | Ph3 | NCT04303780 | Amgen |
| KRASG12C mutant advanced cancers | Ph1/2 | NCT03600883 | |||
| Ph1; with inhibitors targeting PD1, MEK, SHP2, pan-ErbB, PD-L1 or EGFR, or with chemotherapeutic regimen | NCT04185883 | ||||
| Ph1 | NCT04380753 | ||||
| MRTX849 (adagrasib) | KRAS G12C |
KRASG12C mutant advanced cancers | Ph1/2; with TNO155 (SHP2 inhibitor) | NCT04330664 | Mirati |
| Ph1/2; monotherapy and with pembrolizumab, cetuximab or afatinib | NCT03785249 | ||||
| JNJ-74699157 | KRAS G12C | KRASG12C mutant advanced cancers | Ph1 | NCT04006301 | Janssen |
| LY3499446 | KRAS G12C | KRASG12C mutant advanced cancers | Ph1/2; monotherapy and with abemaciclib, cetuximab, erlotinib or docetaxel | NCT04165031 | Eli Lilly |
| iExosomes | KRAS G12D | KRASG12D mutant mPDAC | Ph1 | NCT03608631 | MDACC |
| V941 (mRNA-5671) | mutant KRAS | KRAS mutant mNSCLC, mCRC or mPDAC | Ph1; monotherapy and with pembrolizumab | NCT03948763 | Merck |
| anti-KRAS G12D mTCR PBL | KRAS G12D | KRASG12D mutant cancers | Ph1/2 | NCT03745326 | NCI |
| Anti-KRAS G12V mTCR PBL | KRAS G12V | KRASG12V mutant cancers | Ph1/2 | NCT03190941 | NCI |
| BI 1701963 | SOS1 | KRAS mutant cancers | Ph1; monotherapy and with trametinib | NCT04111458 | Boehringer Ingelheim |
| Rigosertib | RBD domain | KRAS mutant advanced NSCLC (first line treatment refractory) | Ph1/2; with nivolumab | NCT04263090 | Onconova |
| Vemurafenib | BRAF V600E | BRAFV600E mutant metastatic melanoma | Approved | / | Genentech |
| Dabrafenib | BRAF V600E | BRAFV600E/K mutant metastatic melanoma | Approved; monotherapy and with trametinib | / | GlaxoSmithKline |
| Encorafenib | BRAF V600E | BRAFV600E/K mutant metastatic melanoma and mCRC | Approved; with binimetinib (melanoma) or with cetuximab (CRC) | / | Novartis |
| LXH254 | RAF and RAF dimer | MAPK pathway altered advanced cancers | Ph1 | NCT02607813 | Novartis |
| metastatic melanoma | Ph2; with LTT462, trametinib or ribociclib | NCT04417621 | |||
| KRAS or BRAF mutant NSCLC and NRAS mutant melanoma | Ph1; with LTT462, trametinib or ribociclib | NCT02974725 | |||
| PLX8394 | BRAF dimer | BRAF mutant advanced cancers | Ph1/2 | NCT02428712 | Plexxikon |
| Lifirafenib (BGB-283) | BRAF V600E and EGFR | Advanced or treatment refractory cancers | Ph1/2; with PD-0325901 | NCT03905148 | BeiGene |
| Trametinib (GSK1120212) | MEK1/2 | BRAFV600E/K mutant metastatic melanoma | Approved; monotherapy and with dabrafenib | / | GlaxoSmithKline |
| Cobimetinib (GDC-0973) | MEK1 | BRAFV600E/K mutant metastatic melanoma | Approved; with vemurafenib | / | Genentech |
| Binimetinib (ARRY-162) | MEK | BRAFV600E/K mutant metastatic melanoma | Approved; with encorafenib | / | Array |
| Mirdametinib (PD-0325901) | MEK1/2 | KRAS mutant advanced NSCLC |
Ph1/2; with dacomitinib | NCT02039336 | Pfizer |
Ph, Phase; mPDAC, mNSCLC and mCRC, metastatic PDAC, NSCLC and CRC.