TY - JOUR
T1 - Afatinib With Pembrolizumab for Treatment of Patients With Locally Advanced/Metastatic Squamous Cell Carcinoma of the Lung
T2 - The LUX-Lung IO/KEYNOTE 497 Study Protocol
AU - Levy, Benjamin
AU - Paz-Ares, Luis
AU - Bennouna, Jaafar
AU - Felip, Enriqueta
AU - Abreu, Delvys Rodríguez
AU - Isla, Dolores
AU - Barlesi, Fabrice
AU - Molinier, Olivier
AU - Madelaine, Jeannick
AU - Audigier-Valette, Clarisse
AU - Kim, Sang We
AU - Kim, Hye Ryun
AU - Ozguroglu, Mustafa
AU - Erman, Mustafa
AU - Badin, Firas Benyamine
AU - Mekhail, Tarek M.
AU - Scheff, Ronald
AU - Chisamore, Michael J.
AU - Sadrolhefazi, Behbood
AU - Riess, Jonathan W.
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
KW - ErbB family blocker
KW - NSCLC
KW - PD-1
KW - Programmed cell death 1 receptor blocker
KW - Tyrosine kinase inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85061939408&partnerID=8YFLogxK
U2 - 10.1016/j.cllc.2018.12.022
DO - 10.1016/j.cllc.2018.12.022
M3 - Article
C2 - 30808583
AN - SCOPUS:85061939408
SN - 1525-7304
VL - 20
SP - e407-e412
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
IS - 3
ER -