Table 3.
Combinational therapies undergoing clinical trial for KRASG12C mutant cancer patients
| KRASG12C inhibitor | Identifier | Phase | Objective | Current Status |
|---|---|---|---|---|
|
AMG-510 Sotorasib (LUMAKRAS) |
NCT03600883 (CodeBreaK 100) | 1/2 | Estimate maximum tolerated dose (MTD) and/or recommended dose for phase 2 regimen (RP2D) followed by safety and tolerability of sotorasib in combination with anti PD-1/L1 and midazolam (GABA-A receptor agonist) | Active, not recruiting |
| NCT04185883 (CodeBreaK 101) | 1b/2 | Evaluate the safety and tolerability of sotorasib in monotherapy and in combination with AMG 404 (PD-1 inhibitor), trametinib (MEK inhibitor), RMC-4630 (SHP2 inhibitor), afatinib (EGFR inhibitor), pembrolizumab (PD-1 inhibitor), panitumumab (EGFR inhibitor), carboplatin/pemetrexed/docetaxel/paclitaxel (chemotherapy), atezolizumab (PD-L1 inhibitor), everolimus (mTORC1 inhibitor), palbociclib (CDK4/6 inhibitor), MVASI (VEGF inhibitor), TNO155 (SHP2 inhibitor), FOLFIRI (chemotherapy), FOLFOX (chemotherapy, and BI 1701963 (SOS1 inhibitor) | Recruiting | |
| NCT04720976 | 1/2a | Assess the safety and tolerability and determine RP2D of JAB-3312 (SHP2 inhibitor) in combination with binimetinib (MEK inhibitor), pembrolizumab (PD-1 inhibitor), osimertinib (EGFR inhibitor), and sotorasib | Recruiting | |
| NCT05480865 (Argonaut) | 1a/1b | Dose escalation/expansion and optimization of BBP-398 (SHP2 inhibitor) in combination with sotorasib | Recruiting | |
| NCT05074810 (RAMP203) | 1/2 | Safety, tolerability, and efficacy of avutometinib (MEK inhibitor) in combination with sotorasib | Recruiting | |
| NCT05118854 | 2 | Safety and tolerability of sotorasib in combination with chemotherapy (cisplatin/carboplatin) AND pemetrexed (chemotherapy) | Recruiting | |
| NCT05180422 | 1/2 | Dose expansion followed by safety and tolerability of sotorasib in combination with MVASI (VEGF inhibitor) | Recruiting | |
| NCT05374538 | 1a/1b | Dose escalation of VIC-1911 (AURKA inhibitor) as monotherapy or in combination with sotorasib | Recruiting | |
| NCT05313009 | 1b/2 | Dose expansion followed by safety and efficacy of sotorasib in combination with tarloxotinib (EGFR inhibitor) | Recruiting | |
| NCT05638295 | 2 | Testing the use of sotorasib as monotherapy or in combination with panitumumab (EGFR inhibitor) in patients with advanced/metastatic malignant solid KRASG12C mutant cancers | Not yet recruiting | |
| NCT04892017 | 1/2 | Dose escalation/expansion of DCC-3116 (ULK1/2 inhibitor) as monotherapy and in combination with sotorasib and other RAS/MAPK inhibitors in patients with advanced or metastatic solid tumors harboring RAS/MAPK pathway mutations | Recruiting | |
|
MRTX849 Adagrasib (KRAZATI) |
NCT03785249 (KRYSTAL-1) | 1/2 | Evaluate safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of adagrasib in monotherapy and in combination with pembrolizumab (PD-1 inhibitor), cetuximab (EGFR inhibitor) | Recruiting |
| NCT04330664 (KRYSTAL-2) | 1/2 | Dose escalation and expansion followed by safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of adagrasib in combination with TNO155 (SHP2 inhibitor) | Active, not recruiting | |
| NCT04418661 | 1/2 | Dose escalation/expansion followed by safety, tolerance, and efficacy of SAR442720 (SHP2 inhibitor) in combination with adagrasib and pembrolizumab (PD-1 inhibitor) | Active, not recruiting | |
| NCT04613596 (KRYSTAL-7) | 2 | Efficacy and safety of adagrasib monotherapy and in combination with pembrolizumab (PD-1 inhibitor) | Recruiting | |
| 3 | Compares efficacy of adagrasib and pembrolizumab against pembrolizumab and chemotherapy (cisplatin OR carboplatin) | Recruiting | ||
| NCT04975256 (KRYSTAL-14) | 1/1b | Safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of BI 1701963 (SOS1 pan-KRAS inhibitor) in combination with adagrasib | Completed | |
| NCT05178888 (KRYSTAL-16) | 1/1b | Evaluate pharmacodynamics and preliminary clinical activity of adagrasib in combination with palbociclib (CDK4/6 inhibitor) | Active, not recruiting | |
| NCT05375994 (RAMP204) | 1/2 | Safety, tolerability, and efficacy of avutometinib (MEK inhibitor) in combination with adagrasib | Recruiting | |
| NCT05472623 (NeoKan) | 2 | Evaluate clinical safety, feasibility, and efficacy of adagrasib in monotherapy or in combination with nivolumab (PD-1 inhibitor) | Not yet recruiting | |
| NCT05578092 | 1/2 | Evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of MRTX0902 (SOS1 inhibitor) as monotherapy or adagrasib | Recruiting | |
| NCT05609578 (KRYSTAL-17) | 2 | Clinical efficacy and safety of pembrolizumab (PD-1 inhibitor) in combination with adagrasib | Recruiting | |
| GDC-6036 | NCT04449874 | 1a/1b | Dose escalation/expansion, safety, pharmacokinetics, and preliminary activity of GDC-6036 (KRASG12C inhibitor) in monotherapy and in combination with atezolizumab (PD-L1 inhibitor), cetuximab (EGFR inhibitor), bevacizumab (VEGF inhibitor), erlotinib (EGFR), GDC-1971 (SHP2 inhibitor, and inavolisib (PI3K inhibitor) | Recruiting |
| D-1553 (garsorasib) | NCT04585035 | 1/2 | Identify the MTD/RP2D and evaluate the safety and tolerability of D-1553 (KRASG12C inhibitor) as monotherapy or in combination with other standard treatments of solid tumors, NSCLC, or colorectal cancer (CRC) | Recruiting |
| NCT05492045 | 1b/2 | Dose escalation followed by safety, tolerability, pharmacokinetics, and efficacy of D-1553 (KRASG12C inhibitor) in combination with other targeted therapies or immunotherapy | Not yet recruiting | |
| JDQ443 | NCT04699188 (KontRASt-01) | 1b/2 | Dose escalation/expansion assessing safety, anti-tumor activity, tolerability, pharmacokinetics, and pharmacodynamics of JDQ443 (KRASG12C inhibitor) in monotherapy or in combination with TNO155 (SHP2 inhibitor) and tislelizumab (PD-1 inhibitor) | Recruiting |
| NCT05358249 (KontRASt-03) | 1b/2 | Dose escalation followed by safety, tolerability, and anti-tumor activity of backbone JDQ443 (KRASG12C inhibitor) in combination with trametinib (MEK inhibitor), ribociclib (CDK4/6 inhibitor, or cetuximab (EGFR inhibitor) | Recruiting | |
| LYS3537982 | NCT04956640 | 1a/1b | Evaluate safety, tolerability, and preliminary efficacy of LY3537982 (KRASG12C inhibitor) in combination with abemaciclib (CDK4/6 inhibitor), erlotinib (EGFR (PD-1 inhibitor), temuterkib (ERK inhibitor), LY3295668 (AURKA inhibitor), cetuximab (EGFR inhibitor), and TNO155 (SHP2 inhibitor) | Recruiting |
| BI 1823911 | NCT04973163 | 1a/1b | Dose escalation/expansion to investigate the safety, pharmacokinetics and preliminary efficacy of BI 1823911 (KRASG12C inhibitor) in monotherapy or in combination with BI 1701963 (SOS1 inhibitor) and midazolam (GABA-A receptor agonist) | Recruiting |
| JAB-21822 | NCT05002270 | 1/2 | Dose escalation/expansion followed by safety and tolerability of JAB-21822 (KRASG12C inhibitor) as monotherapy or in combination with cetuximab (EGFR inhibitor) | Recruiting |
| NCT05288205 | 1/2a | Dose escalation/expansion evaluating efficacy and safety of JAB-21822 (KRASG12C inhibitor) in combination with JAB-3312 (SHP2 inhibitor) | Recruiting | |
| IBI351 | NCT05504278 | 1b/2 | Evaluate efficacy and safety of IBI351 (KRASG12C inhibitor) in combination with sintilimab (PD-1 inhibitor), chemotherapy (pemetrexed and/or cisplatin/carboplatin), and cetuximab (EGFR inhibitor) | Not yet recruiting |