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Bending the Curve Trial by Trial
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KRYSTAL-12

Phase 3 Study of MRTX849 (Adagrasib) vs Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

Phase 3N = 453NCT04685135

Population
KRAS G12C-mutated locally advanced or metastatic NSCLC previously treated with both platinum-based chemotherapy and anti-PD-1 or PD-L1 therapy
Design
Randomised (2:1), open-label phase 3 trial at 230 centres in 22 countries: adagrasib 600 mg orally twice daily versus docetaxel 75 mg/m2 intravenously every 3 weeks, in KRAS G12C-mutated locally advanced or metastatic NSCLC previously treated with platinum-based chemotherapy and anti-PD-1 or PD-L1 therapy. Primary endpoint progression-free survival by blinded independent central review.
Primary endpoint
PFS
Arms
  • Docetaxel (control, n = 152): Docetaxel 75 mg/m2 intravenously every 3 weeks
  • Adagrasib (experimental, n = 301): Adagrasib 600 mg orally twice daily
People
Barlesi F
PFSHR 0.58 (95% CI 0.45–0.76)Δ median PFS+1.7 months
Show the numbers
Results reported for KRYSTAL-12
EndpointAnalysisAdagrasibDocetaxelEffect
PFSPFS assessed by blinded independent central reviewprimarymedian follow-up 7.2 monthsBarlesi 2025median 5.5 months (4.5–6.7)median 3.8 months (2.7–4.7)HR 0.58 (95% CI 0.45–0.76)P<0.0001
Results reported for KRYSTAL-12
EndpointAnalysisAdagrasibDocetaxelEffect
PFSPFS assessed by blinded independent central reviewprimarymedian follow-up 7.2 monthsBarlesi 2025median 5.5 months (4.5–6.7)median 3.8 months (2.7–4.7)HR 0.58 (95% CI 0.45–0.76)P<0.0001
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.580.45–0.76
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%024681012Months (modelled)
  • Docetaxel (control)
  • Adagrasib (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsDocetaxelAdagrasib
0100.0%100.0%
357.9%68.5%
727.9%41.4%
1016.1%28.4%
147.8%17.1%
Primary publication: Barlesi F, Yao W, Duruisseaux M, Doucet L, Martínez AA, Gregorc V, et al. Adagrasib versus docetaxel in KRAS(G12C)-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial. Lancet. 2025;406(10503):615-626. PubMedDOI

Appears in

Sources

  1. Barlesi F, Yao W, Duruisseaux M, Doucet L, Martínez AA, Gregorc V, et al. Adagrasib versus docetaxel in KRAS(G12C)-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial. Lancet. 2025;406(10503):615-626.

    PubMedDOI