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.

Autor: Levy B; Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, Washington, DC. Electronic address: blevy11@jhmi.edu., Paz-Ares L; Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain., Bennouna J; Department of Pneumology, Thoracic Oncology, University Hospital-Nantes, Nantes, France., Felip E; Medical Oncology Department, Vall d'Hebron Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain., Abreu DR; Department of Medical Oncology, Gran Canaria University Hospital, Las Palmas de Gran Canaria, Spain., Isla D; Department of Medical Oncology, University Hospital Lozano Blesa, Zaragoza, Spain., Barlesi F; Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France., Molinier O; Pneumology, Centre Hospitalier Le Mans, Le Mans, France., Madelaine J; Pulmonology Department, Caen University Hospital, Caen, France., Audigier-Valette C; Service de Pneumologie, Centre Hospitalier Sainte Musse, Toulon, France., Kim SW; Asan Medical Center, Seoul, South Korea., Kim HR; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea., Ozguroglu M; Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey., Erman M; Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey., Badin FB; Hematology and Oncology, Baptist Health Medical Group, Lexington, KY., Mekhail TM; Florida Hospital Cancer Institute, Orlando, FL., Scheff R; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell College of Medicine, New York, NY., Chisamore MJ; Merck & Co, Inc, Rahway, NJ., Sadrolhefazi B; Boehringer Ingelheim Canada Ltd, Burlington, Ontario, Canada., Riess JW; UC Davis Comprehensive Cancer Center, Sacramento, CA.
Jazyk: angličtina
Zdroj: Clinical lung cancer [Clin Lung Cancer] 2019 May; Vol. 20 (3), pp. e407-e412. Date of Electronic Publication: 2019 Jan 04.
DOI: 10.1016/j.cllc.2018.12.022
Abstrakt: 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.
(Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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