378MO - EMPOWER-Lung 1: Phase III first-line (1L) cemiplimab monotherapy vs platinum-doublet chemotherapy (chemo) in advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%

Background

EMPOWER-Lung 1 is a multicentre, open-label, global, phase III study of cemiplimab, an anti–PD-1, in patients (pts) with treatment-naïve stage IIIB, IIIC or IV squamous or non-squamous NSCLC with PD-L1 expressed in ≥50% of tumour cells.

Methods

Pts were randomised 1:1 to receive cemiplimab 350 mg Q3W IV or investigator’s choice of chemo. Crossover (CO) from chemo to cemiplimab was allowed following progression. The primary endpoints were overall survival (OS) and progression-free survival (PFS) per blinded Independent Review Committee. A prespecified interim analysis was performed after 50% of OS events. Data are presented per intention-to-treat (ITT) and in a PD-L1 ≥50% ITT population which comprised only pts with PD-L1 ≥50% by 22C3 per instruction for use (after recommended retesting in some pts). Data cut-off was 1 March 2020.

Results

In the ITT population (median follow-up: 13.1 months), median OS was 22.1 months (95% CI: 17.7–not evaluable [NE]) with cemiplimab (n=356) vs 14.3 months (95% CI: 11.7–19.2) with chemo (n=354; HR, 0.68; 95% CI: 0.53–0.87; P=0.002). Median PFS was 6.2 months (95% CI: 4.5–8.3) with cemiplimab vs 5.6 months (95% CI: 4.5–6.1) with chemo (HR, 0.59; 95% CI: 0.49–0.72; P<0.0001). In the PD-L1 ≥50% ITT population (median follow-up: 10.8 months), median OS was not reached (95% CI: 17.9–NE) with cemiplimab (n=283) vs 14.2 months (95% CI: 11.2–17.5) with chemo (n=280; HR, 0.57; 95% CI: 0.42–0.77; P=0.0002). Median PFS was 8.2 months (95% CI: 6.1–8.8) with cemiplimab vs 5.7 months (95% CI: 4.5–6.2) with chemo (HR, 0.54; 95% CI: 0.43–0.68; P<0.0001). CO rate to cemiplimab was 73.9%. In the ITT population, cemiplimab was associated with higher response rate (36.5% vs 20.6%), longer median duration of response (21.0 months vs 6.0 months) and lower rates of Grade ≥3 adverse events regardless of attribution (37.2% vs 48.5%) compared to chemo.

Conclusions

In this study, 1L cemiplimab monotherapy significantly improved OS and PFS vs chemo in pts with advanced NSCLC with PD-L1 ≥50%, despite high CO rate, providing rationale for cemiplimab as a new treatment option for this patient population.

Clinical trial identification

NCT03088540.

Editorial acknowledgement

Medical writing support was provided by Emmanuel Ogunnowo, PhD of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc. and Sanofi.

Funding

Regeneron Pharmaceuticals, Inc. and Sanofi.

Disclosure

A. Sezer: Research grant/Funding (institution), outside the submitted work: Roche; Research grant/Funding (institution), outside the submitted work: Merck Sharp & Dohme; Research grant/Funding (institution), outside the submitted work: Merck Serono; Research grant/Funding (institution), outside the submitted work: AstraZeneca; Research grant/Funding (institution), outside the submitted work: Lily; Research grant/Funding (institution), outside the submitted work: Novartis; Research grant/Funding (institution), outside the submitted work: JohnsonJohnson; Research grant/Funding (institution), outside the submitted work: Regeneron Pharmaceuticals, Inc.; Research grant/Funding (institution), outside the submitted work: Sanofi. M. Gümüş: Honoraria (institution), outside the submitted work: Roche; Honoraria (institution), outside the submitted work: Merck Sharp & Dohme; Honoraria (institution), outside the submitted work: Gen İlaç; Honoraria (institution), outside the submitted work: Novartis. N. Rizvi: Advisory/Consultancy, outside the submitted work: AbbVie; Advisory/Consultancy, outside the submitted work: Apricity; Advisory/Consultancy, outside the submitted work: AstraZeneca; Advisory/Consultancy, outside the submitted work: Boehringer; Advisory/Consultancy, outside the submitted work: Calithera; Advisory/Consultancy, outside the submitted work: Dracen; Advisory/Consultancy, outside the submitted work: Editas; Advisory/Consultancy, outside the submitted work: EMD Sorono; Advisory/Consultancy, outside the submitted work: G1 Therapeutics; Advisory/Consultancy, outside the submitted work: Genentech, Gilead and GSK; Advisory/Consultancy, outside the submitted work: Illumina; Advisory/Consultancy, outside the submitted work: Lilly; Advisory/Consultancy, outside the submitted work: Merck; Advisory/Consultancy, outside the submitted work: Neogenomics; Advisory/Consultancy, outside the submitted work: Novartis; Advisory/Consultancy, Shareholder/Stockholder/Stock options, outside the submitted work: Brooklyn ImmunoTherapeutics; Advisory/Consultancy, outside the submitted work: Takeda; Advisory/Consultancy, Shareholder/Stockholder/Stock options, outside the submitted work: Bellicum; Shareholder/Stockholder/Stock options, outside the submitted work: Gritstone; Licensing/Royalties, Patent (pending) filed by MSKCC, in the form of royalties, on “determinants of cancer response to immunotherapy, (PCT/US2015/062208)” licensed to Personal Genome Diagnostics: MSKCC. S. Li; S. Lee; G. Gullo: Shareholder/Stockholder/Stock options, Full/Part-time employment: Regeneron Pharmaceuticals, Inc. I. Lowy; P. Rietschel: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.