Lapatinib Plus Trametinib in KRAS Mutant NSCLC

Phase I/II Study With Lapatinib Plus Trametinib in Patients With Metastatic KRAS Mutant Non-small Cell Lung Cancer

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02230553

Acronym

M14LTK

Enrollment

Registered

2014-09-03

Start date

2014-10-07

Completion date

2019-08-06

Last updated

2025-07-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Colorectal Cancer

Brief summary

This is an open-label phase I/II multi-center study consisting of two parts. Part A of this study is designed to identify the recommended phase 2 dose (RP2D) of lapatinib combined with trametinib in patients with metastatic KRASm and PIK3CA wild-type (PIK3CAwt) non-small cell lung cancer (NSCLC). Part B is designed to perform a randomized comparison of the lapatinib-trametinib combination versus standard of care therapy in patients with metastatic KRASm/PIK3CAwt NSCLC.

Interventions

DRUGLapatinib

DRUGtrametinib

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Histological or cytological proof of metastatic NSCLC; for PART B: treated with first line therapy for metastatic disease only. * Written documentation of a known pathogenic KRAS (exon 2, 3 or 4) mutation and PIK3CA wild-type (exon 9 and 20) * Age ≥ 18 years * Able and willing to give written informed consent * WHO performance status of 0 or 1 (part A and B)

Exclusion criteria

* Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment. * History of another primary malignancy * Symptomatic or untreated leptomeningeal disease * Symptomatic brain metastasis * History of interstitial lung disease or pneumonitis * Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients * Retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), or a history of uveitis, retinal vein occlusion, central serous retinopathy, or retinal detachment * Patients with left ventricular ejection fraction (LVEF) \< 50%

Design outcomes

Primary

Measure	Time frame
Incidence rate of dose-limiting toxicities	1.5 years
progression free survival	2.5 years
overall response rate	2.5 years

Secondary

Measure	Time frame
Time to response	2.5 years
Incidence and severity of adveres events	2.5 years
Overall survival	3 years
Plasma concentration	2.5 years
Duration of response	2.5 years

Countries

Netherlands

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026