Afatinib With Pembrolizumab for Treatment of Patients With Locally Advanced/Metastatic Squamous Cell Carcinoma of the Lung: The LUX-Lung IO/KEYNOTE 497 Study Protocol.
Afatinib
/ therapeutic use
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Carcinoma, Squamous Cell
/ drug therapy
ErbB Receptors
/ antagonists & inhibitors
Female
Humans
Immunotherapy
/ methods
Lung Neoplasms
/ drug therapy
Male
Mutation
/ genetics
Neoplasm Staging
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Survival Analysis
Treatment Outcome
ErbB family blocker
NSCLC
PD-1
Programmed cell death 1 receptor blocker
Tyrosine kinase inhibitor
Journal
Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
12
09
2018
accepted:
31
12
2018
pubmed:
28
2
2019
medline:
4
4
2020
entrez:
28
2
2019
Statut:
ppublish
Résumé
Afatinib is a selective, irreversible ErbB family blocker that has shown survival benefit in lung squamous-cell carcinoma (SCC) patients. Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody to the programmed cell death 1 (PD-1) receptor, has also shown survival benefit in lung SCC. Concurrent inhibition of the PD-1 and epidermal growth factor receptor (EGFR) pathways represents a rational approach to improve responses and delay the onset of treatment resistance in lung SCC. This phase II, open-label, single-arm study (NCT03157089) is designed to assess the efficacy and safety of afatinib in combination with pembrolizumab in patients with stage IIIB/IV lung SCC that has progressed during/after first-line platinum-based chemotherapy. Eligible patients must have ≥1 target lesion (as per Response Evaluation Criteria in Solid Tumors version 1.1) and must have not received previous immune checkpoint inhibitor/EGFR-targeted therapy. The recommended phase II dose (RP2D) and safety profile will be determined during a safety run-in with oral afatinib (starting dose, 40 mg/d) with intravenous pembrolizumab (200 mg every 3 weeks). In the main study, all patients will receive afatinib at the RP2D with pembrolizumab until disease progression, unacceptable toxicity, or for up to 35 cycles. The primary end point is objective response (complete + partial response). Other end points include disease control, duration of objective response, progression-free survival, overall survival, tumor shrinkage, RP2D, and pharmacokinetics. Exploratory biomarker analysis will be performed. This study is being conducted in the United States, Spain, France, South Korea, and Turkey. Enrollment commenced in September 2017, with a target of 50 to 62 patients.
Sections du résumé
BACKGROUND
Afatinib is a selective, irreversible ErbB family blocker that has shown survival benefit in lung squamous-cell carcinoma (SCC) patients. Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody to the programmed cell death 1 (PD-1) receptor, has also shown survival benefit in lung SCC. Concurrent inhibition of the PD-1 and epidermal growth factor receptor (EGFR) pathways represents a rational approach to improve responses and delay the onset of treatment resistance in lung SCC.
TRIAL DESIGN
This phase II, open-label, single-arm study (NCT03157089) is designed to assess the efficacy and safety of afatinib in combination with pembrolizumab in patients with stage IIIB/IV lung SCC that has progressed during/after first-line platinum-based chemotherapy. Eligible patients must have ≥1 target lesion (as per Response Evaluation Criteria in Solid Tumors version 1.1) and must have not received previous immune checkpoint inhibitor/EGFR-targeted therapy. The recommended phase II dose (RP2D) and safety profile will be determined during a safety run-in with oral afatinib (starting dose, 40 mg/d) with intravenous pembrolizumab (200 mg every 3 weeks). In the main study, all patients will receive afatinib at the RP2D with pembrolizumab until disease progression, unacceptable toxicity, or for up to 35 cycles. The primary end point is objective response (complete + partial response). Other end points include disease control, duration of objective response, progression-free survival, overall survival, tumor shrinkage, RP2D, and pharmacokinetics. Exploratory biomarker analysis will be performed. This study is being conducted in the United States, Spain, France, South Korea, and Turkey. Enrollment commenced in September 2017, with a target of 50 to 62 patients.
Identifiants
pubmed: 30808583
pii: S1525-7304(19)30001-4
doi: 10.1016/j.cllc.2018.12.022
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Afatinib
41UD74L59M
pembrolizumab
DPT0O3T46P
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Banques de données
ClinicalTrials.gov
['NCT03157089']
Types de publication
Clinical Trial Protocol
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e407-e412Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.