NCT03516214

EGF816 and Trametinib in Patients With Non-small Cell Lung Cancer Harboring Activating EGFR Mutations

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 Remark: According to Version V02_0 of the Protocol, Patients May Also be Eligible if EGFR TKI-treatment naïve, EGFR p.T790M-negative at Progression While on EGFR TKI Therapy or After Progression While on Osimertinib Treatment

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: University of Cologne · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The aim of this trial is to identify the maximum tolerated dose (MTD)/recommended phase II dose (RP2D), to define pharmacokinetic (PK) parameters and the preliminary efficacy of a continuous treatment with EGF816 and trametinib in locally advanced or metastatic (stage IIIB or IV) lung cancer patients with activating mutations in the epithelial growth factor receptor (EGFR).

Detailed description

The population of interest for this trial is defined by patients with non-small cell lung cancer (NSCLC) harbouring the sensitizing EGFR mutations del19 or p.L858R. Patients may be enrolled in first- or later lines of therapy and independently of the prior (approved) EGFR inhibitor administered and independently of the EGFR p.T790M-status. Those individuals whose tumors harbour high-level amplifications of MET or other EGFR mutations except for del19, p.L858R or p.T790M will be excluded from the trial. The molecular status must have been determined in a biopsy collected at progression to the last systemic and prior to the initiation of the trial treatment The aim of the trial is to identify the maximum tolerated dose (MTD)/recommended phase II dose (RP2D) for a continuous treatment with the 3rd generation EGFR inhibitor EGF816 and the MEK inhibitor trametinib. The recommendations for dose level escalations will be based on an "up-and-down" design proposed by Storer, 1989. The dose limiting toxicity (DLT) period comprises the first 28 days of treatment with EGF816 and trametinib at the designated dose level (Cycle 1). PK parameters of the combination treatment will be assessed for every dose level in every patient during the dose-escalation part. Preliminary efficacy of EGF816 and trametinib in the trial population will be assessed by RECIST (v1.1) analysis of scheduled CT scans (every 8 weeks or as clinically indicated. Throughout the study blood samples will be collected to monitor cell free plasma DNA (cfDNA). Patients who develop resistance upon treatment with the study drugs will undergo a rebiopsy to identify potential mechanisms of resistance.

Conditions

• Bronchial Neoplasms

Interventions

Type	Name	Description
DRUG	EGF816	Continuous oral treatment (once daily) with the 3rd generation EGFR inhibitor EGF816.
DRUG	Trametinib	Continuous oral treatment (once daily) with the MEK inhibitor trametinib.

Timeline

• Start date: 2018-04-25
• Primary completion: 2022-09-30
• Completion: 2023-11-27
• First posted: 2018-05-04
• Last updated: 2024-02-15

Locations

7 sites across 2 countries: Germany, Spain

Regulatory

• FDA-regulated drug study