Table 1.
Direct KRASG12C Inhibitors in Clinical Trials
| Agent | Company | Identifier | Phase | Status | Details |
|---|---|---|---|---|---|
| JNJ-74699157 (ARS-3248) | Janssen Research & Development, LLC | NCT04006301 | 1 | Completed | Non-randomized, open-label study examining monotherapy in patients with advanced solid tumors (e.g., NSCLC, CRC) harboring the KRASG12C mutation. Results unavailable. |
| AMG510 (sotorasib) | Amgen | NCT03600883 | 1/2 | Recruiting | CodeBreaK100. Randomized, open-label study examining AMG510 alone and in combination with anti (PD-1/L1) in patients with advanced solid tumors with KRAS p.G12C mutation, and AMG510 alone in patients with naïve (i.e., previously untreated) advanced NSCLC with KRAS p.G12C mutation. |
| NCT04185883 | 1b/2 | Recruiting | CodeBreaK101. Non-randomized, open-label study assessing AMG510 alone and in combination with other anti-cancer therapies in patients with advanced solid tumors with KRAS p.G12C mutation. Treatment arms include monotherapy in patients with advanced NSCLC with brain metastases; in combination with trametinib (MEK1/2 inhibitor), AMG 404 (PD-1 inhibitor), RMC-4630 (SHP2 inhibitor), palbociclib (CDK4/6 inhibitor), or everolimus (mTOR inhibitor) in patients with advanced solid tumors; in combination with afatinib (pan-ErbB inhibitor), pembrolizumab (PD-1 inhibitor), AMG 404 (PD-1 inhibitor), atezolizumab (PD-L1 inhibitor), or chemotherapy (carboplatin, pemetraxed, and docetaxel) in patients with advanced NSCLC; in combination with panitumumab (EGFR inhibitor) +/− chemotherapy (FOLFIRI), trametinib and panitumumab, or bevacizumab-awwb and chemotherapy (FOLFIRI or FOLFOX) in patients with advanced CRC. | ||
| NCT04380753 | 1 | Recruiting | CodeBreaK105. Open-label study assessing monotherapy in patients of Chinese ancestry with advanced/metastatic solid tumors with KRAS p.G12C mutation. | ||
| NCT04303780 | 3 | Active, not recruiting | CodeBreaK200. Randomized, open-label study comparing monotherapy vs. docetaxel in patients with previously treated advanced/metastatic NSCLC with KRAS p.G12C mutation. | ||
| NCT04933695 | 2 | Not yet recruiting | CodeBreaK201. Randomized, open-label study investigating monotherapy in patients with Stage IV NSCLC with KRASG12C mutation and PD-L1 TPS < 1%, stratified by STK11 co-mutation. | ||
| NCT04625647 | 2 | Not yet recruiting | Lung-MAP Treatment Trial sub-study (S1900E). Open-label study evaluating monotherapy in patients with stage IV or recurrent non-squamous NSCLC with KRASG12C mutation. | ||
| NCT04667234 | Expanded access (Available) | Study provides expanded access to and characterize the safety profile of AMG 510 in patients with previously treated locally advanced/unresectable/metastatic NSCLC with KRAS p.G12C mutation in a real-world setting. | |||
| MRTX849 (adagrasib) | Mirati Therapeutics Inc. | NCT03785249 | 1/2 | Recruiting | KRYSTAL-1. Non-randomized, open-label clinical trial evaluating MRTX849 alone in patients with advanced/metastatic solid tumors with KRASG12C mutation, in combination with pembrolizumab or afatinib in patients with NSCLC with KRASG12C mutation, or in combination with cetuximab in patients with CRC with KRASG12C mutation. |
| NCT04330664 | 1/2 | Recruiting | KRYSTAL 2. Non-randomized, open-label study investigating MRTX849 in combination with TNO155 (SHP2 inhibitor) in patients with advanced solid tumors (NSCLC or CRC) with KRASG12C mutation. | ||
| NCT04613596 | 2 | Recruiting | KRYSTAL-7. Open-label study examining MRTX849 in combination with pembrolizumab (anti-PD1 antibody) in patients with advanced NSCLC with KRASG12C mutation. | ||
| NCT04793958 | 3 | Recruiting | KRYSTAL-10. Randomized, open-label study comparing combination therapy MRTX849 and cetuximab (anti-EGFR antibody) vs. chemotherapy (mFOLFOX6 or FOLFIRI) in patients with advanced/metastatic CRC with KRASG12C mutation. | ||
| NCT04685135 | 3 | Recruiting | KRYSTAL-12. Randomized, open-label study comparing monotherapy with docetaxel (taxane) in patients with advanced/metastatic NSCLC with KRASG12C mutation. | ||
| NCT04975256 | 1/1b | Recruiting | KRYSTAL 14. Non-randomized, open-label study assessing MRTX849 in combination with BI 1701963 (SOS1 pan-KRAS inhibitor) in patients with advanced/metastatic solid malignancies (NSCLC or CRC) with KRASG12C mutation. | ||
| LY3499446 | Eli Lilly and Company | NCT04165031 | 1/2 | Terminated | Randomized, open label study comparing LY3499446 alone and in combination with abemaciclib, cetuximab, or erlotinib vs. docetaxel in patients with advanced/metastatic solid tumors with KRASG12C mutation. Study was terminated due to unexpected toxicity finding. |
| LY3537982 | Eli Lilly and Company | NCT04956640 | 1 | Not yet recruiting | Non-randomized, open-label study investigating LY3537982 alone and in combination with abemaciclib, erlotinib, sintilimab, temuterkib, LY3295668 (aurora A kinase inhibitor), or cetuximab in patients with KRASG12C mutant solid tumors. |
| GDC-6036 | Genentech, Inc. | NCT04449874 | 1 | Recruiting | Non-randomized, open-label study investigating GDC-6036 alone and in combination with atezolizumab, cetuximab, bevacizumab, erlotinib, or GDC-1971 (SHP2 inhibitor) in patients with advanced/metastatic solid tumors with KRASG12C mutation. |
| D-1553 | InventisBio Inc. | NCT04585035 | 1/2 | Recruiting | Non-randomized, open-label study evaluating D-1553 alone and in combination with other drugs used in standard treatment of solid tumors (not specified) in patients with advanced/metastatic solid tumors, including NSCLC and CRC, with KRASG12C mutation. |
| JDQ443 | Novartis Pharmaceuticals | NCT04699188 | 1b/2 | Recruiting | Non-randomized, open-label study assessing monotherapy and in combination with TNO155 (SHP2 inhibitor) and/or spartalizumab (anti-PD1 antibody) in patients with advanced (metastatic or unresectable) KRASG12C mutant solid tumors. |
| BI 1823911 | Boehringer Ingelheim | NCT04973163 | 1a/1b | Not yet recruiting | Non-randomized, open-label study investigating BI 1823911 alone and in combination with BI 1701963 (SOS1::KRAS pan-KRAS inhibitor) in patients with advanced/metastatic solid tumors (e.g., NSCLC, CRC, pancreatic cancer, or cholangiocarcinoma) with KRASG12C mutation. |
Abbreviations: NSCLC non-small cell lung cancer, CRC colorectal cancer