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Confirmed that the KRAS pill adagrasib beats chemotherapy after first-line treatment, though the gain is modest.
KRYSTAL-12, trial NCT04685135 sponsored by Bristol Myers Squibb through Mirati and reported in 2024, confirmed that the KRAS G12C inhibitor adagrasib beats docetaxel after first-line treatment in KRAS G12C-mutant non-small-cell lung cancer, though the gain is modest. It randomised 453 patients, met its primary progression-free survival endpoint by blinded review and showed higher objective and intracranial response rates than chemotherapy, supporting full approval and the second-line role of G12C inhibitors, while overall survival was not yet significantly different. OnCo links it to KRAS as a target and to the bottleneck of undruggable drivers, and its result is consistent with CodeBreaK 200 for sotorasib, where neither trial showed a survival benefit. Whether G12C inhibitors help more in first-line combinations is the open question. Adagrasib has its own page.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
453 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (BICR)primary | Adagrasib | 301 | 5.5 months | 0.58 (0.45 to 0.76) | <0.0001 | link |
| Docetaxel | 152 | 3.8 months |
Shares Adagrasib, KRAS G12C-mutant non-small-cell lung cancer, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, KRAS & RAS inhibitors.
Shares Adagrasib, KRAS G12C-mutant non-small-cell lung cancer, KRAS & RAS inhibitors, Non-small-cell lung cancer.
Shares KRAS G12C-mutant non-small-cell lung cancer, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, KRAS & RAS inhibitors, The undruggable drivers.
Shares Adagrasib, KRAS G12C-mutant non-small-cell lung cancer, KRAS & RAS inhibitors, Non-small-cell lung cancer.
Shares Adagrasib, KRAS G12C-mutant non-small-cell lung cancer, KRAS & RAS inhibitors, Non-small-cell lung cancer.
Shares Adagrasib, KRAS G12C-mutant non-small-cell lung cancer, KRAS & RAS inhibitors.
Shares Adagrasib, KRAS G12C-mutant non-small-cell lung cancer, KRAS & RAS inhibitors, KRAS.
Shares Adagrasib, KRAS G12C-mutant non-small-cell lung cancer, KRAS & RAS inhibitors, KRAS.