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

Benjamin Levy, Luis Paz-Ares, Jaafar Bennouna, Enriqueta Felip, Delvys Rodríguez Abreu, Dolores Isla, Fabrice Barlesi, Olivier Molinier, Jeannick Madelaine, Clarisse Audigier-Valette, Sang We Kim, Hye Ryun Kim, Mustafa Ozguroglu, Mustafa Erman, Firas Benyamine Badin, Tarek M. Mekhail, Ronald Scheff, Michael J. Chisamore, Behbood Sadrolhefazi, Jonathan Riess

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalClinical lung cancer
DOIs
StatePublished - Jan 1 2019

Fingerprint

Squamous Cell Carcinoma
Lung
Safety
Epidermal Growth Factor Receptor
Survival
Programmed Cell Death 1 Receptor
Therapeutics
Republic of Korea
Turkey
Platinum
Spain
Disease-Free Survival
France
Disease Progression
Immunoglobulins
Cell Death
Pharmacokinetics
Biomarkers
Monoclonal Antibodies
BIBW 2992

Keywords

  • ErbB family blocker
  • NSCLC
  • PD-1
  • Programmed cell death 1 receptor blocker
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

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. / Levy, Benjamin; Paz-Ares, Luis; Bennouna, Jaafar; Felip, Enriqueta; Abreu, Delvys Rodríguez; Isla, Dolores; Barlesi, Fabrice; Molinier, Olivier; Madelaine, Jeannick; Audigier-Valette, Clarisse; Kim, Sang We; Kim, Hye Ryun; Ozguroglu, Mustafa; Erman, Mustafa; Badin, Firas Benyamine; Mekhail, Tarek M.; Scheff, Ronald; Chisamore, Michael J.; Sadrolhefazi, Behbood; Riess, Jonathan.

In: Clinical lung cancer, 01.01.2019.

Research output: Contribution to journalArticle

Levy, B, Paz-Ares, L, Bennouna, J, Felip, E, Abreu, DR, Isla, D, Barlesi, F, Molinier, O, Madelaine, J, Audigier-Valette, C, Kim, SW, Kim, HR, Ozguroglu, M, Erman, M, Badin, FB, Mekhail, TM, Scheff, R, Chisamore, MJ, Sadrolhefazi, B & Riess, J 2019, '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', Clinical lung cancer. https://doi.org/10.1016/j.cllc.2018.12.022
Levy, Benjamin ; Paz-Ares, Luis ; Bennouna, Jaafar ; Felip, Enriqueta ; Abreu, Delvys Rodríguez ; Isla, Dolores ; Barlesi, Fabrice ; Molinier, Olivier ; Madelaine, Jeannick ; Audigier-Valette, Clarisse ; Kim, Sang We ; Kim, Hye Ryun ; Ozguroglu, Mustafa ; Erman, Mustafa ; Badin, Firas Benyamine ; Mekhail, Tarek M. ; Scheff, Ronald ; Chisamore, Michael J. ; Sadrolhefazi, Behbood ; Riess, Jonathan. / 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. In: Clinical lung cancer. 2019.
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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

PY - 2019/1/1

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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.

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