KRAS encodes a small GTPase of the RAS family, one of the most frequently mutated oncogenes across human cancers — particularly pancreatic (~90%), colorectal (~45%), and NSCLC (~30%) adenocarcinomas. Historically considered undruggable due to its smooth surface and picomolar GTP affinity.
The therapeutic landscape inflected sharply in 2013–2021 following covalent inhibitor strategies targeting the G12C switch-II pocket. Two approvals to date: sotorasib (Amgen · 2021) and adagrasib (Mirati / BMS · 2022). Next-generation programmes target pan-KRAS, RAS(ON), G12D, and G12V variants.
| Variant | Trials (active) | Companies | Patents 24m | Lead Candidate | Trajectory |
|---|---|---|---|---|---|
| G12C | 148 | 22 | 1,247 | Sotorasib · Adagrasib | ▬▬▬▬▬▬▬▬ SATURATING |
| G12D | 37 | 14 | 892 | MRTX1133 (Revolution) | ▬▬▬▬▬▬▬ ACCELERATING |
| G12V | 11 | 8 | 312 | RMC-9805 (Revolution) | ▬▬▬▬▬ EMERGING |
| Pan-KRAS | 19 | 11 | 541 | RMC-6236 · BI 1701963 | ▬▬▬▬▬▬ ACCELERATING |
| RAS(ON) multi | 6 | 3 | 184 | RMC-6236 (tri-complex) | ▬▬▬ EARLY |
| Company | Jurisdiction | Active Trials | Lead Asset | Phase |
|---|---|---|---|---|
| Amgen Inc. | US · SEC | 42 | Sotorasib (Lumakras) | APPROVED |
| Bristol Myers Squibb (Mirati acq. 2023) |
US · SEC | 38 | Adagrasib (Krazati) | APPROVED |
| Revolution Medicines | US · SEC | 14 | RMC-6236 · RMC-9805 | PH 3 |
| Kumquat Biosciences | US | 6 | KQB-445 | PH 1 |
| Erasca, Inc. | US · SEC | 5 | ERAS-0015 | PH 1 |
| Boehringer Ingelheim | DE | 9 | BI 1701963 | PH 2 |
| Jiangsu Hengrui | CN | 7 | HRS-4642 | PH 1 |