# KRYSTAL-12

Source: https://onco.cc/trials/krystal-12/  
OnCo record `krystal-12` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Confirmed that the KRAS pill adagrasib beats chemotherapy after first-line treatment, though the gain is modest.

## Summary

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-06
- Registry id: NCT04685135
- Phase: 3
- Setting: Previously treated KRAS G12C NSCLC: adagrasib vs docetaxel
- Sponsor: BMS (Mirati)
- Enrolled: 453
- Result: PFS HR 0.58.
- Outcomes: Progression-free survival (BICR): Adagrasib 5.5 months vs Docetaxel 3.8 months, HR 0.58
- Replication: Consistent with CodeBreaK 200 (sotorasib vs docetaxel, PFS HR 0.66); neither trial showed an OS benefit.

## Sources

- ClinicalTrials.gov NCT04685135: https://clinicaltrials.gov/study/NCT04685135

## Connected records

- cancers: [KRAS G12C-mutant non-small-cell lung cancer](https://onco.cc/cancers/kras-g12c-nsclc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [KRAS & RAS inhibitors](https://onco.cc/technologies/kras-inhibitors/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- drugs: [Adagrasib](https://onco.cc/drugs/adagrasib/)
- key papers: [KRYSTAL-12 plain language summary: adagrasib for non-small-cell lung cancer with KRAS G12C mutations](https://onco.cc/key-papers/paper-krystal-12-plain-language-summary-future-oncol-2026/)
- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- roadmaps: [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)

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