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

Phase 3 Active not recruiting 453 enrolled Mirati Therapeutics Inc.

RandomizedParallel-groupOpen-labelTreatment

Summary

This Phase 3 study will evaluate the efficacy of the investigational agent MRTX849 (adagrasib) versus docetaxel in patients who have been previously treated for metastatic NSCLC with a KRAS G12C mutation.

Timeline

Start: 2021-02-23
Primary completion: 2023-12-30
Completion: 2026-07-02

Outcome

Met primary endpoint

registry analysis (superiority test); Adagrasib vs Docetaxel; p <0.0001; Hazard Ratio (HR) 0.58 (95% CI 0.45 to 0.76); Log Rank NCT04685135 ↗

paper Adagrasib demonstrated a statistically significant improvement in progression-free survival over docetaxel PMID 40783289 ↗

release “KRYSTAL-12 Confirmatory Trial Evaluating KRAZATI (adagrasib) Meets Primary Endpoint of Progression-Free Survival” bms.com ↗

Publications

Barlesi F, Yao W, Duruisseaux M, Doucet L, Martinez AA, Gregorc V, Juan-Vidal O, Lu S, De Bondt C, de Marinis F, Linardou H, Kim YC, Jotte R, Felip E, Lo Russo G, Reck M, Michenzie MF, Yang W, Meade JN, Korytowsky B, Mok TSK; KRYSTAL-12 Investigators. Adagrasib versus docetaxel in KRASG12C-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial. Lancet. 2025 Aug 9;406(10503):615-626. doi: 10.1016/S0140-6736(25)00866-9.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Adagrasib	Small molecule	600 mg	Oral
Comparator	Docetaxel	Small molecule	75 mg/m2	Intravenous