Table 1.
Clinical trials targeting KRAS
| Target | Agent | Combinations | Study phase |
Tumor type | Recruitment status | Trial number |
|---|---|---|---|---|---|---|
| BRAF, CRAF | LXH-254 | None | I | Advanced solid tumors harboring MAPK pathway alterations | Active, not recruiting | NCT02607813 |
| BRAF, CRAF | LXH-254 | Rineterkib (RAF/ERK inhibitor); trametinib (MEK inhibitor); ribociclib (CDK4/6 inhibitor); EGF816 (EGFR inhibitor); dabrafenib (BRAF mutant inhibitor) | I, II | Unresectable or metastatic melanoma; EGFR-mutant NSCLC | Recruiting; active, not recruiting | NCT04417621; NCT02974725; NCT03333343; NCT04294160 |
| ERK | LY3214996; GDC-0994; ulixertinib; MK-8353 | None | I, II | Acute myeloid leukemia; locally advanced or metastatic solid tumors; metastatic uveal melanoma; acute myelogenous leukemia or myelodysplastic syndromes | Recruiting; completed; terminated | NCT04081259; NCT01875705; NCT04488003; NCT03417739; NCT02296242; NCT01358331 |
| ERK | LY3214996 | RMC-4630 (SHP2-inhibitor); abemaciclib (CDK4/6 inhibitor); hydroxychloroquine (autophagy inhibitor) | I, II | Metastatic KRAS mutant cancers; solid tumors harboring pathogenic alterations in BRAF, RAF1, MEK1/2, ERK1/2, and NF1 | Not yet recruiting | NCT04916236; NCT04956640; NCT04534283; NCT04616183; NCT04391595; NCT04386057 |
| ERK | GDC-0994 | Cobimetinib (MEK inhibitor) | I | Locally advanced or metastatic solid tumors | Completed | NCT02457793 |
| ERK | Ulixertinib | Hydroxychloroquine (autophagy inhibitor); palbociclib (CDK4/6 inhibitor) | I, II | Advanced MAPK-mutated gastrointestinal adenocarcinomas; advanced pancreatic and other solid tumors | Recruiting | NCT041452973; NCT03454035 |
| ERK | MK-8353 | Selumetinib (MEK inhibitor); pembrolizumab (anti–PD-1 ab) | I | Advanced malignancies | Completed; active, not recruiting | NCT03745989; NCT02972034 |
| KRAS | AZD4785 | None | I | Advanced solid tumors | Completed | NCT03101839 |
| KRAS-G12C | Sotorasib | None | I, II | KRAS-G12C–mutant advanced/metastatic solid tumors | Recruiting; not yet recruiting | NCT04380753; NCT04625647; NCT04667234; NCT04933695 |
| KRAS-G12C | Sotorasib | Docetaxel (microtubule inhibitor); pembrolizumab (anti–PD-1 ab) | I, II, III | KRAS-G12C–mutant advanced/metastatic solid tumors | Active, not recruiting; recruiting | NCT04303780; NCT03600883; NCT04613596 |
| KRAS-G12C | Adagrasib | Docetaxel (microtubule inhibitor); pembrolizumab (anti–PD-1 ab); cetuximab (anti-EGFR ab); afatinib (pan-EGFR inhibitor); TNO155 (SHP2 inhibitor) | I, II, III | KRAS-G12C–mutant advanced/metastatic solid tumors | Recruiting | NCT04685135; NCT03785249; NCT04330664; NCT04793958 |
| KRAS-G12C | GDC-6036 | Atezolizumab (anti–PD-L1 ab); cetuximab (anti-EGFR ab); bevacizumab (anti-VEGF ab); erlotinib (EGFR inhibitor) | I | KRAS-G12C–mutant advanced/metastatic solid tumors | Recruiting | NCT04449874 |
| KRAS-G12C | D-1553 | Standard treatment | I | KRAS-G12C–mutant advanced/metastatic solid tumors | Recruiting | NCT04585035 |
| KRAS-G12C | JNJ-74699157 | Standard treatment | I | KRAS-G12C–mutant advanced/metastatic solid tumors | Completed | NCT04006301 |
| KRAS-G12C | LY3499446 | Abemaciclib (CDK4/6 inhibitor); cetuximab (anti-EGFR ab); erlotinib (EGFR inhibitor); docetaxel (microtubule inhibitor) | I, II | KRAS-G12C–mutant advanced/metastatic solid tumors | Terminated | NCT04165031 |
| KRAS-G12D | siG12D-LODER | Gemcitabine + nab-paclitaxel; FOLFIRINOX | II | Advanced pancreatic cancer | Recruiting | NCT01676259 |
| MEK | Cobimetinib |
Belvarafenib (RAF inhibitor) |
I | Advanced or metastatic solid tumors | Recruiting | NCT03284502 |
| MEK | Trametinib | LXH254 (RAF inhibitor) | I | NSCLC or melanoma | Recruiting | NCT02974725 |
| MEK | Pimasertib | None | I | N-RAS–mutated locally advanced or metastasis malignant cutaneous melanoma | Recruiting | NCT01693068, NCT00982865 |
| MEK | Pimasertib | SAR405838 (MDM2 antagonist) | I | Advanced solid tumors | Completed | NCT01985191 |
| MEK | Mirdametinib | Lifirfenib | I | Advanced or refractory solid tumors | Recruiting | NCT03905148 |
| p110α | Alpelisib | Capecitabine (nucleoside metabolic inhibitor); paclitaxel (microtubule inhibitor) | I | Patients with PIK3CA mutant metastatic colorectal cancer; PIK3CA-altered metastatic/recurrent gastric cancer | Not yet recruiting | NCT04753203; NCT04526470 |
| p110α | GDC-0077 | Entrectinib (pan-TRK inhibitor) | I | Breast cancer and advanced solid tumors | Recruiting | NCT04632992 |
| RAF | PLX8394; TAK-580 | None | I, II | Advanced unresectable solid tumors; low-grade glioma | Recruiting | NCT02428712; NCT03429803 |
| RAF | Belvarafenib | None | I | Solid tumors | Completed | NCT02405065 |
| RAF | Belvarafenib | Cobimetinib (MEK inhibitor); cetuximab (anti-EGFR ab); atezolizumab (anti–PD-L1 ab) | I | Advanced or metastatic solid tumors; NRAS-mutant advanced melanoma | Recruiting | NCT03284502; NCT04835805 |
| RAF, EGFR | Lifirfenib | None | I | Solid tumors | Completed | NCT02610361; NCT03641586 |
| RAF, EGFR | Lifirfenib | Mirdametinib (MEK inhibitor) | I | NSCLC with confirmed KRAS mutations | Recruiting | NCT04294160 |
| SHP2 | BBP-398; JAB-3068; RMC-4630; RLY-1971; JAB-3312; SH3809 | None | I, II | Advanced or metastatic solid tumors | Recruiting | NCT04528836; NCT03565003; NCT03518554; NCT03634982; NCT04252339; NCT04121286; NCT04045496; NCT04843033 |
| SHP2 | RMC-4630 | LY3214996 (ERK inhibitor); cobimetinib (MEK inhibitor); osimertinib (EGFR inhibitor) | I, II | Advanced or metastatic solid tumors | Not yet recruiting; recruiting | NCT04916236; NCT03989115 |
| SHP2 | ERAS-601 | Cobimetinib (MEK inhibitor) | I | Advanced or metastatic solid tumors | Recruiting | NCT04670679 |
| SHP2 | TNO155 | Nazartinib (EGFR inhibitor); spartalizumab (anti–IL-1β antibody); ribociclib (CDK4/6 inhibitor); adagrasib (KRAS-G12C inhibitor); JDQ443 (KRAS-G12C inhibitor) | I, II | Advanced solid tumors | Recruiting | NCT03114319; NCT04000529; NCT04330664; NCT04699188 |
| SOS1 | BI 1701963 | Trametinib (MEK inhibitor); BI 3011441 (MEK inhibitor); irinotecan (topoisomerase I inhibitor) | I | Advanced or metastatic solid tumors | Recruiting | NCT04111458; NCT04835714; NCT04627142 |