Status: Active Trial | Marker: EGFR

Title

An open-label, multicenter, phase I dose-escalation trial of EGF816 and trametinib in patients with non-small cell lung cancer and acquired EGFR p.T790M positive resistance to 1st or 2nd generation EGFR TKI therapy

Study Number

NCT03516214

Indication

Patients with advanced non-small cell lung cancer harbouring sensitizing EGFR mutations (EGFR del19 or EGFR p.L858R) with progression upon treatment with 1st or 2nd generation EGFR TKI and acquired resistance mutation EGFR p.T790M

Primary objective

The EATON study (EGF816 and trametinib in EGFR T790M-positive NSCLC) is a European multicentre Phase I study investigating two tyrosine kinase inhibitors EGF816 (3rd generation EGFR inhibitor) and trametinib (MEK inhibitor). Patients who have EGFR-positive bronchogenic carcinoma and who are on a regimen of erlotinib, gefitinib or afatinib may participate in the study if there is an EGFR p.T790M mutation. Patients already receiving osimertinib or other 3rd generation EGFR inhibitors or who have no EGFR p.T790M mutation cannot participate. The aim of the combination of the two test substances is to increase the number of patients who respond to the therapy with 3rd generation EGFR inhibitors and to delay the development of resistance.

In- and exclusion Criteria

Inclusion Criteria:
• Histologically documented, locally advanced or recurrent (stage IIIB who are not eligible for combined modality treatment) or metastatic (stage IV) non-small cell lung cancer with documented EGFR p.L858R/del-mutation, EGFR p.T790M-mutation and absence of a high-level MET amplification
• Progression while on treatment with first-/second-generation EGFR-TKIs
• Prior treatment with any investigational agent known to inhibit EGFR (mutant or wild-type) or any 3rd generation EGFR TKI or any MEK/ERK inhibitor
• Prior treatment with more than 3 lines of antineoplastic therapy in the advanced setting including EGFR TKI treatment.
• No brain metastases. However, if radiation therapy and/or surgery has been completed at least 4 weeks prior to screening for the trial and evaluation by CT (with contrast enhancement) or MRI at study baseline demonstrates the disease to be stable and if the patient remains asymptomatic and off steroids, then patients with brain metastases may be enrolled.
• No presence or history of carcinomatous meningitis.
• No history of hepatitis B (HBV) or hepatitis C (HCV) or positive result in mandatory testing for acute or chronic hepatitis B or hepatitis C
• No known HIV infection or history of HIV infection independent from the cellular immune status

Study design

Open-label, multicenter, phase I dose-escalation trial of EGF816 and trametinib

Responsibilities

LCGC – University Hospital of Cologne

Trial Centre

University Hospital of Cologne
Dep. I of Internal Medicine
Phone: +49 221 478 87008
Fax: +49 221 478 87010
lungenkrebs@uk-koeln.de

Principal investigator

Prof. Dr. J. Wolf

Last Update: 28. June 2018