Table 2.
Clinical Trials of KRAS G12C-Targeted Therapy on KRAS Mutant Tumors.
| Drug Name | Treatment Strategy | Stage | Patient Characteristics | Number of Patients | Initiation Year | NCT Number |
|---|---|---|---|---|---|---|
| Sotorasib (AMG 510) |
Monotherapy | Phase 2 | Advanced NSCLC with KRAS G12C mutations | 116 | 2021 | NCT04625647 |
| Monotherapy | Phase 1–2 | Advanced solid tumors with KRAS G12C mutations | 793 | 2018 | NCT03600883 | |
| Monotherapy | Phase 2 | Stage IV NSCLC with KRAS G12C mutations without prior treatment | 170 | 2022 | NCT04933695 | |
| Monotherapy | Phase 2 | Stage Ib-IIIA resectable NSCLC with KRAS G12C mutations | 25 | 2022 | NCT05400577 | |
| Monotherapy | Phase 2 | Stage III unresectable NSCLC with KRAS G12C mutations | 43 | 2022 | NCT05398094 | |
| Monotherapy | Phase 1 | Advanced solid tumors with KRAS G12C mutations | 12 | 2020 | NCT04380753 | |
| Monotherapy | Phase 2 | Stage III unresectable NSCLC with KRAS G12C mutations | 43 | 2022 | NCT05398094 | |
| Monotherapy (VS Docetaxel) | Phase 3 | Advanced NSCLC with KRAS G12C mutations | 345 | 2020 | NCT04303780 | |
| Combined with Tarloxotinib (pan-ERBB inhibitor) | Phase 1–2 | Advanced NSCLC with KRAS G12C mutations | 30 | 2022 | NCT05313009 | |
| Combined with BBP-398 (SHP2 inhibitor) | Phase 1 | Advanced solid tumors with KRAS G12C mutations | 85 | 2022 | NCT05480865 | |
| Combined with VS-6766 (RAF/MEK inhibitor) | Phase 1–2 | Advanced NSCLC with KRAS G12C mutations | 53 | 2022 | NCT05074810 | |
| Combined with targeted therapy, chemotherapy, or immunotherapy | Phase 1–2 | Advanced Solid tumors with KRAS G12C mutations | 1054 | 2019 | NCT04185883 | |
| Combined targeted therapy, chemotherapy, or immunotherapy |
Phase 1–2 | Advanced solid tumors with KRAS G12C mutations | 1054 | 2019 | NCT04185883 | |
| Combined with Panitumumab (anti-EGFR mAb) vs. Trifluridine and Tipiracil (chemotherapy) + Regorafenib (multi-kinase inhibitor *) | Phase 3 | Advanced CRC with KRAS G12C mutations | 153 | 2022 | NCT05198934 | |
| Combined with MVASI (antiangiogenic drug) | Phase 1–2 | Advanced NSCLC with KRAS G12C mutations and Brain metastasis | 43 | 2022 | NCT05180422 | |
| Combined with Cisplatin or Carboplatin and Pemetrexed (chemotherapy) | Phase 2 | Stage IIA-IIIB resectable non-squamous NSCLC with KRAS G12C mutations | 27 | 2022 | NCT05118854 | |
| Adagrasib (MRTX849) |
MRTX monotherapy or combined with Pembrolizumab (anti-PD-1 ICI)/Cetuximab (anti-EGFR IgG1 mAb)/Afatinib (EGFR TKI) | Phase 1–2 | Advanced or metastatic cancer with KRAS G12C mutations | 740 | 2019 | NCT03785249 |
| Monotherapy | Phase 2 | Advanced or metastatic NSCLC with KRAS G12C mutations | 116 | 2022 | NCT03785249 | |
| MRTX849 monotherapy or combined with Pembrolizumab (anti-PD-1 ICI) | Phase 2 | Advanced or metastatic NSCLC with KRAS G12C mutations | 250 | 2020 | NCT04613596 | |
| Monotherapy vs. Docetaxel (chemotherapy) | Phase 3 | Advanced or metastatic NSCLC | 340 | 2021 | NCT04685135 | |
| MRTX849 combined with Cetuximab (anti- EGFR IgG1 mAb) vs. mFOLFOX6 and FOLFIRI (chemotherapy) | Phase 3 | Advanced CRC with KRAS G12C mutations | 420 | 2021 | NCT04793958 | |
| Combined with VS-6766 (RAF-MEK inhibitor) | Phase 1–2 | Advanced NSCLC with KRAS G12C mutations | 85 | 2022 | NCT05375994 | |
| JAB-21822 | Monotherapy | Phase 1–2 | Advanced solid tumors with KRAS G12C mutations | 144 | 2021 | NCT05009329 |
| Monotherapy or combined with Cetuximab (anti-EGFR IgG1 mAb) | Phase 1–2 | Advanced solid tumors with KRAS G12C mutations | 100 | 2021 | NCT05002270 | |
| Combined with Cetuximab (anti-EGFR IgG1 mAb) | Phase 1–2 | Advanced solid tumors with KRAS G12C mutations | 62 | 2022 | NCT05194995 | |
| Combined with JAB-3312 (SHP2 inhibitor) | Phase 1–2 | Advanced solid tumors with KRAS G12C mutations | 124 | 2022 | NCT05288205 | |
| JDQ443 | Monotherapy | Phase 3 | Advanced NSCLC with KRAS G12C mutations | 360 | 2022 | NCT05132075 |
| Monotherapy or combined with TNO155 (SHP2 inhibitor) or tislelizumab (anti-PD-1 ICI) or TNO155 + tislelizumab | Phase 1–2 | Advanced solid tumors with KRAS G12C mutations | 425 | 2021 | NCT04699188 | |
| D3S-001 | Monotherapy | Phase 1 | Advanced solid tumors with KRAS G12C mutations | 98 | 2022 | NCT05410145 |
| GFH925 | Monotherapy | Phase 1–2 | Advanced solid tumors with KRAS G12C mutations | 128 | 2021 | NCT05005234 |
| YL-15293 | Monotherapy | Phase 1–2 | Advanced solid tumors with KRAS G12C mutations | 55 | 2021 | NCT05119933 |
| JNJ-74699157 | Monotherapy | Phase 1 | Advanced solid tumors with KRAS G12C mutations | 10 | 2019 | NCT04006301 |
| GDC-6036 | Monotherapy or combined with chemotherapy, immunotherapy, etc. | Phase 1 | Advanced solid tumors with KRAS G12C mutations | 498 | 2020 | NCT04449874 |
| LY3537982 | Monotherapy or combined with targeted therapy, immunotherapy, etc. | Phase 1 | Advanced solid tumors with KRAS G12C mutations | 360 | 2021 | NCT04956640 |
| RMC-6236 | Monotherapy (KRAS G12X inhibitor) | Phase 1 | Advanced solid tumors with KRAS mutations | 141 | 2022 | NCT05379985 |
* NSCLC: non-small cell lung cancer; CRC: colorectal cancer; SHP2: Src homology2 (SH2) domain-containing protein tyrosine phosphatase (PTPase); EGFR: epidermal growth factor receptor; MEK: mitogen-activated extracellular signal-regulated kinase; IgG1: immunoglobulin G1; mAb: monoclonal antibody; ICI: immune checkpoint inhibitor; TKI: Tyrosine kinase inhibitor.