An Open-label Study of GSK1120212 Compared With Docetaxel in Stage IV KRAS-mutant Non-small Cell Lung Cancer

Summary

This is a phase II, open-label, multicenter, randomized study to evaluate the efficacy and safety of GSK1120212 compared with docetaxel in the second line setting for subjects with locally advanced or metastatic (Stage IV) Non-small cell lung cancer (NSCLC) harboring a KRAS mutation who have failed one platinum-containing chemotherapy regimen. A small subset of NSCLC subjects harboring BRAF, NRAS, or MEK1 mutations will be randomized in addition to the primary KRAS population, for exploratory purposes.

Timeline

Start

2011-09

Primary completion

2012-09

Completion

2013-09

Outcome

Missed primary endpoint

registry GSK1120212 2 mg in RP vs Docetaxel 75 mg/m^2 in RP; p = 0.5197; Hazard Ratio (HR) 1.14 (95% CI 0.75 to 1.75); Log Rank; NCT01362296 ↗

paper the comparison of trametinib versus docetaxel for PFS crossed the futility boundary. PMID 25722381 ↗

Publications

• Blumenschein GR Jr, Smit EF, Planchard D, Kim DW, Cadranel J, De Pas T, Dunphy F, Udud K, Ahn MJ, Hanna NH, Kim JH, Mazieres J, Kim SW, Baas P, Rappold E, Redhu S, Puski A, Wu FS, Janne PA. A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)dagger. Ann Oncol. 2015 May;26(5):894-901. doi: 10.1093/annonc/mdv072. Epub 2015 Feb 26.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Docetaxel	Small molecule	75 mg/m2	Intravenous
Subject	Trametinib	Small molecule	2 mg	Oral

Indications