Table 1.
Select recent clinical trials targeting KRAS and downstream signaling pathways.
| Trial ID | Trial Title | Target(s) | Cancer(s) | Mechanism |
|---|---|---|---|---|
| NCT01274624 | Study of REOLYSIN in Combination With FOLFIRI and Bevacizumab in FOLFIRI Naïve Patients With KRAS Mutant Metastatic Colorectal Cancer | Activated RAS | CRC | Stimulates lysis of tumor cells and induces antitumor immunity |
| NCT03808558 | Phase 2 Study of TVB-2640 in KRAS Non-Small Cell Lung Carcinomas | FASN | NSCLC | Disrupts tumor lipid rafts and RAS localization |
| NCT03600883 | A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreak 100) | KRAS G12C | NSCLC, solid tumors | Binds to cysteine residue in KRAS G12C mutations holding protein in inactive form and prevents downstream signaling |
| NCT03785249 | Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1 | KRAS G12C | NSCLC, CRC, other solid tumors | Modifies mutant cysteine 12 in a GDP-bound state and inhibits KRAS dependent signaling |
| NCT04006301 | First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation | KRAS G12C | NSCLC, solid tumors | Binds to KRAS G23C and holds the protein in inactive form, preventing downstream signaling |
| NCT03948763 | A Study of mRNA-5671/V941 as Monotherapy and in Combination With Pembrolizumab (V941-001) | KRAS G12D, G12V, G13D, and G12C | NSCLC, CRC, pancreatic | Induces T-cell dependent immune responses to destroy tumors presenting KRAS mutations |
| NCT04132505 | Binimetinib and Hydroxychloroquine in Treating Patients With KRAS Mutant Metastatic Pancreatic Cancer | MEK, Autophagy | pancreatic | Binimetinib: Noncompetitive ATP inhibitor preventing MEK signaling. Hydroxychloroquine: Inhibits autophagy to avoid metabolism of Binimetinib |
| NCT03040986 | Selumetinib Sulfate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer With KRAS G12R Mutations | MEK | pancreatic | Potent and selective inhibitor against MEK1/2 and KRAS dependent signaling |
| NCT02642042 | Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer | MEK | NSCLC | Trametinib: Inhibits MEK signaling downstream of KRAS. Docetaxel: Chemotherapeutic |
| NCT02101788 | Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer | MEK | ovarian, peritoneal | Inhibits MEK signaling downstream of KRAS |
| NCT02613650 | A Trial of mFOLFIRI With MEK162 in Patients With Advanced RAS (HRAS, NRAS, or KRAS) Positive Metastatic Colorectal Cancers | MEK | CRC | MEK162: Uncompetitive ATP inhibitor suppresses the activity of MEK1/2 and KRAS downstream signaling. mFOLFIRI: Chemotherapeutic |
| NCT03704688 | Trial of Trametinib and Ponatinib in Patients With KRAS Mutant Advanced Non-Small Cell Lung Cancer | MEK, Multi-tyrosine Kinase | NSCLC | Trametinib: Inhibits MEK signaling downstream of KRAS. Ponatinib: Targets multiple tyrosine kinases and inhibits signaling |
| NCT03829410 | Onvansertib in Combination With FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer Patients With a KRAS Mutation | PLK1, VEGF | CRC | Onvansertib: Selectively inhibits PLK1 causing mitotic arrest and cell death. Bevacizumab: Binds to VEGF and reduces blood supply to tumors. FOLFIRI: Chemotherapeutic |
| NCT04111458 | A Study to Test Different Doses of BI 1701963 Alone and Combined With Trametinib in Patients With Different Types of Advanced Cancer (Solid Tumours With KRAS Mutation) | SOS1, MEK | NSCLC, solid tumors | BI 1701963: Inhibits KRAS binding to SOS1, leading to KRAS inactivation. Trametinib: Inhibits MEK signaling downstream of KRAS |