Table 1.
Selected KRAS-directed therapies
| Strategy and target | Agent | Phase of development |
|---|---|---|
| Mutant-specific direct KRAS inhibitors | ||
| KRASG12C | Sotorasib (AMG 510) | Approved for previously treated advanced-stage KRASG12C-mutant NSCLC; further clinical trials ongoing (NCT03600883, NCT04185883, NCT04303780, NCT04933695, NCT04625647, NCT05398094, NCT05074810, NCT04380753, NCT05311709, NCT05054725, NCT05400577, NCT05180422, NCT04667234, NCT05198934, NCT05374538, NCT05313009, NCT05118854, NCT05273047, NCT05251038, NCT04892017, NCT04959981, NCT04720976) |
| Adagrasib (MRTX849) | Clinical trials (NCT03785249, NCT04330664, NCT04613596, NCT04793958, NCT04685135, NCT05162443, NCT05375994, NCT05263986, NCT04975256, NCT05178888, NCT04418661) | |
| D-1553 | Clinical trials (NCT04585035, NCT05383898, NCT05379946) | |
| JDQ443 | Clinical trials (NCT04699188, NCT05132075, NCT05358249, NCT05329623) | |
| RG6330 (GDC-6036) | Clinical trials (NCT04449874, NCT03178552) | |
| LY3537982 | Clinical trials (NCT04956640) | |
| BI 1823911 | Clinical trials (NCT04973163) | |
| JAB-21822 | Clinical trials (NCT05009329, NCT05194995, NCT05002270, NCT05276726, NCT05288205) | |
| JNJ-74699157 (ARS-3248) | Clinical trials (NCT04006301) | |
| MK-1084 | Clinical trials (NCT05067283) | |
| ARS-1620 | Preclinical studies | |
| ARS-853 | Preclinical studies | |
| RM-018 | Preclinical studies | |
| RMC-6291 | Preclinical studies | |
| KRASG12D | MRTX1133 | Preclinical studies |
| JAB-22000 | Preclinical studies | |
| RMC-9805 (RM-036) | Preclinical studies | |
| KRASG13C | RMC-8839 | Preclinical studies |
| KRASG12V | JAB-23000 | Preclinical studies |
| KRASMULTI | JAB-23400 | Preclinical studies |
| Pan-RAS inhibitors | ||
| RASMULTI | RMC-6236 | Clinical trials (NCT05379985) |
| BBP-454 | Preclinical studies | |
| SOS1 inhibitors | ||
| SOS1 | BI 1701963 | Clinical trials (NCT04973163, NCT04111458, NCT04975256, NCT04835714, NCT04627142) |
| RMC-5845 | Preclinical studies | |
| BAY-293 | Preclinical studies | |
| BI-3406 | Preclinical studies | |
| SDGR5 | Preclinical studies | |
| SHP2 inhibitors | ||
| SHP2 | RMC-4630 (SAR442720) | Clinical trials (NCT03634982, NCT05054725, NCT04418661, NCT03989115, NCT04916236, NCT04185883) |
| TNO155 | Clinical trials (NCT03114319, NCT04000529, NCT04294160, NCT04956640, NCT04330664, NCT04292119, NCT04699188, NCT04185883) | |
| GDC-1971 | Clinical trials (NCT04449874) | |
| JAB-3068 | Clinical trials (NCT03518554, NCT03565003, NCT04721223) | |
| JAB-3312 | Clinical trials (NCT04045496, NCT04121286, NCT04720976, NCT05288205) | |
| SHP099 | Preclinical studies | |
| RMC-4550 | Preclinical studies | |
| RAS degraders | ||
| KRASG12C | LC-2 (PROTAC) | Preclinical studies |
| KRASG12C, KRASG12D, KRASG12V and KRASQ61H | K27-SPOP | Preclinical studies |
| RAS toxins | ||
| Pan-RAS | RRSP–DTB | Preclinical studies |
| Adoptive cell therapy | ||
| KRASG12V | Specific TCRs | Clinical trials (NCT04146298) |
| KRASG12D | Specific TCRs | Preclinical studies |
| Cancer vaccines | ||
| KRASG12C, KRASG12D, KRASG12V and KRASG13D | mRNA-5671/V941 | Clinical trials (NCT03948763) |
| KRASG12C, KRASG12V, KRASG12D, KRASG12A, KRASG13D or KRASG12R | Mutant KRAS-targeted long-peptide vaccine | Clinical trials (NCT04117087) |
| KRASG12C, KRASG12V, KRASG12D or KRASG12R | mDC3/8-KRAS vaccine | Clinical trials (NCT03592888) |
| KRASG12D or KRASG12R | ELI-002 2P | Clinical trials (NCT04853017) |
| KRAS siRNAs | ||
| Various mutant KRAS mRNAs | Various nanoparticle-based technologies | Preclinical studies |
| KRASG12D mRNA | iExosomes | Clinical trials (NCT03608631) |
NSCLC, non-small-cell lung cancer; PROTAC, proteolysis targeting chimera; siRNA, small interfering RNA; TCR, T cell receptor.