First-Line Cemiplimab for Locally Advanced NSCLC: Updated Subgroup Analyses From the EMPOWER-Lung 1 and EMPOWER-Lung 3 Trials

Ewa Kalinka; Igor Bondarenko; Miranda Gogishvili; Tamar Melkadze; Ana Baramidze; Ahmet Sezer; Tamta Makharadze; Saadettin Kilickap; Mahmut Gümüş; Konstantin Penkov; Davit Giorgadze; Mustafa Özgüroğlu; Ruben G W Quek; Debra A G McIntyre; Eric Kim; Frank Seebach; Jean-Francois Pouliot

doi:10.1016/j.jtocrr.2025.100947

First-Line Cemiplimab for Locally Advanced NSCLC: Updated Subgroup Analyses From the EMPOWER-Lung 1 and EMPOWER-Lung 3 Trials

JTO Clin Res Rep. 2025 Dec 22;7(4):100947. doi: 10.1016/j.jtocrr.2025.100947. eCollection 2026 Apr.

Authors

Ewa Kalinka¹, Igor Bondarenko², Miranda Gogishvili³, Tamar Melkadze⁴, Ana Baramidze⁴, Ahmet Sezer⁵, Tamta Makharadze⁶, Saadettin Kilickap⁷, Mahmut Gümüş⁸, Konstantin Penkov⁹, Davit Giorgadze¹⁰, Mustafa Özgüroğlu¹¹, Ruben G W Quek¹², Debra A G McIntyre¹², Eric Kim¹², Frank Seebach¹², Jean-Francois Pouliot¹²

Affiliations

¹ Polish Mother's Memorial Hospital Research Institute, Łódź, Poland.
² Department of Oncology and Medical Radiology, Dnipropetrovsk Medical Academy, Dnipro, Ukraine.
³ High Technology Medical Centre, Tbilisi, Georgia.
⁴ Research Institute of Clinical Medicine, Todua Clinic, Tbilisi, Georgia.
⁵ Department of Medical Oncology, Medicalpark Seyhan Hospital, Adana, Turkey.
⁶ LTD High Technology Hospital Medical Center, Batumi, Georgia.
⁷ Department of Medical Oncology, Istinye University Faculty of Medicine, Istanbul, Turkey.
⁸ Department of Medical Oncology, School of Medicine, Istanbul Medeniyet University, Istanbul, Turkey.
⁹ Private Medical Institution Euromedservice, St Petersburg, Russia.
¹⁰ State Budgetary Healthcare Institution of Omsk Region, Omsk, Russia.
¹¹ Cerrahpaşa Medical Faculty, Istanbul University-Cerrahpaşa, Istanbul, Turkey.
¹² Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.

Abstract

Introduction: Patients with unresectable locally advanced NSCLC who are not candidates for concurrent chemoradiation represent an unmet medical need. We report long-term results for this patient subgroup from two phase III trials.

Methods: We analyzed data from patients with locally advanced NSCLC in the EMPOWER-Lung 1 (NCT03088540) and EMPOWER-Lung 3 (NCT03409614) studies. In EMPOWER-Lung 1, patients were randomized 1:1 to first-line (1L) cemiplimab monotherapy or chemotherapy with more than or equal to 50% programmed death-ligand 1 expression. In EMPOWER-Lung 3, patients were randomized 2:1 to 1L cemiplimab plus chemotherapy or chemotherapy, regardless of programmed death-ligand 1 expression.

Results: Patients with locally advanced NSCLC constituted 15% of the overall study populations. With cemiplimab monotherapy, the overall survival (OS) was improved versus chemotherapy (median 26.1 versus 13.9 mo; hazard ratio [HR]: 0.67, 95% confidence interval [CI]: 0.38-1.17) and progression-free survival (8.1 versus 6.2 mo; HR: 0.56, 95% CI: 0.34-0.95). With cemiplimab plus chemotherapy, the OS was improved versus chemotherapy alone (24.1 versus 13.8 mo; HR: 0.50, 95% CI: 0.27-0.95) and progression-free survival (12.5 versus 6.2 mo; HR: 0.34, 95% CI: 0.19-0.61). Treatment-emergent adverse events grade more than or equal to 3 occurred in 37.8% (cemiplimab) and 53.7% (chemotherapy) in EMPOWER-Lung 1 and in 46.7% (cemiplimab plus chemotherapy) and 25.0% (chemotherapy) in EMPOWER-Lung 3. Favorable patient-reported outcomes were observed with cemiplimab monotherapy than chemotherapy; no significant patient-reported outcomes favoring chemotherapy were observed in either study.

Conclusions: This subgroup analysis supports the clinical benefit of 1L cemiplimab as monotherapy or combined with chemotherapy in patients with unresectable locally advanced NSCLC (not candidates for definitive chemoradiotherapy).

Keywords: Cemiplimab; Immune checkpoint inhibitors; Immunotherapy; Locally advanced non–small cell lung cancer; PD-L1.