Gefitinib plus tremelimumab combination in refractory non-small cell lung cancer patients harbouring EGFR mutations: The GEFTREM phase I trial.

Abstract

INTRODUCTION:

A phase I open-label multicentre study was initiated to evaluate the association of tremelimumab with gefitinib in EGFR-mutant NSCLC patients who progressed after first-generation EGFR-TKI. Here we provide the efficacy data from the entire cohort.

MATERIAL AND METHODS:

Patients with advanced EGFR-mutant NSCLC with progression after response to EGFR-TKI were enrolled. Study treatment was gefitinib 250 mg daily and tremelimumab at 3 dose levels: 3, 6 and 10 mg/kg IV Q4W for 6 cycles followed by Q12W until progression or unacceptable toxicity. The primary objective was safety and tolerability, and to establish a RP2D.

RESULTS:

Between January 2014 and July 2015, 27 patients (21 in the escalating dose cohort and 6 in expansion cohort) received at least one dose of tremelimumab. DLTs occurred in 4 patients: 1 at 3 mg/kg (one grade 3 diarrhoea), 1 at 6 mg/kg (one grade 3 diarrhoea) and 2 at 10 mg/kg (one grade 3 diarrhoea and one grade 3 AST/ALT increase) of tremelimumab. Grade 3 TRAE occurred in 22 patients (81%), most frequently diarrhoea (30%) and ALT/AST increase (15%). Stable disease was the best overall response in 72% patients, with median PFS of 2.2 months (95% CI, 1.8-4.2). All patients discontinued treatment, most frequently due to disease progression (63% of patients).

CONCLUSION:

The recommended dose of tremelimumab in combination with gefitinib in EGFR-mutant NSCLC patients was 3 mg/kg. The gastrointestinal toxicity and the limited efficacy data prevented further evaluation of this combination. (GEFTREM; clinical trial number NCT02040064).

• Authors: Mariona Riudavets, Marie Naigeon, Matthieu Texier, Miriam Dorta, Fabrice Barlesi, Julien Mazieres, Andrea Varga, Lydie Cassard, Lisa Boselli, Jonathan Grivel, Maud NgoCamus, Ludovic Lacroix, Laura Mezquita, Benjamin Besse, Nathalie Chaput, David Planchard
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 166 Pg. 255-264 (04 2022) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 34953624 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• EGFR protein, human
• ErbB Receptors
• tremelimumab
• Gefitinib

Topics

• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Diarrhea (chemically induced)
• ErbB Receptors (genetics)
• Gefitinib (therapeutic use)
• Humans
• Lung Neoplasms (chemically induced, drug therapy, genetics)
• Mutation