FDA Approves Cemiplimab as First-Line Treatment for Advanced, High PD-L1 NSCLC

February 22, 2021
Hannah Slater

The approval of cemiplimab in non–small cell lung cancer was supported by results from the phase 3 EMPOWER-Lung 1 trial that investigated its use as monotherapy in the first-line setting compared with platinum-doublet chemotherapy in patients with locally advanced or metastatic disease whose tumor cells expressed PD-L1.

The FDA has approved the PD-1 inhibitor cemiplimab-rwlc (Libtayo) as a first-line treatment option for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with 50% or more PD-L1 expression, according to the agent’s developer, Regeneron.1

The FDA also approved the PD-L1 IHC 22C3 pharmDx assay for expanded use in this patient population to identify those with greater than 50% PD-L1 expression who are suitable for treatment with cemiplimab, announced the assay‘s developer Agilent Technologies. Currently, PD-L1 IHC 22C3 pharmDx is the only companion diagnostic with FDA approval for this use.2

“The approval of Libtayo to treat first-line advanced non–small cell lung cancer with high PD-L1 expression means physicians and patients have a potent new treatment option against this deadly disease,” Naiyer Rizvi, MD, Price Family Professor of Medicine, Director of Thoracic Oncology and Co-director of Cancer Immunotherapy at Columbia University Irving Medical Center, as well as a steering committee member of the trial, said in press release. “Notably, Libtayo was approved based on a pivotal trial where most [patients receiving chemotherapy] crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases, or who had locally advanced disease and were not candidates for definitive chemoradiation. This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice.”

The approval was supported by results from the open-label, randomized, multicenter phase 3 EMPOWER-Lung 1 trial (NCT03088540) that investigated the first-line use of cemiplimab-rwlc monotherapy compared with platinum-doublet chemotherapy in patients with locally advanced or metastatic NSCLC whose tumors expressed PD-L1 in 50% or more of cells, including those whose cancers had confirmed expression by the PD-L1 IHC 22C3 pharmDx kit.3 Results from the trial were presented at the 2020 European Society for Medical Oncology (ESMO) Virtual Congress in September 2020.4

Patients included in the trial were randomized 1:1 to receive either cemiplimab-rwlc at a dose of 350 mg administered intravenously every 3 weeks for up to 108 weeks or an investigator-selected, standard-of-care, platinum-based, doublet chemotherapy regimen for 4 to 6 cycles.

The co-primary end points of the study were overall survival (OS) and progression-free survival (PFS), and secondary end points included overall response rate (ORR), duration of response (DOR), health-related quality of life (HRQoL), and safety.

At a median follow-up of 13.1 months in the ITT population, the median OS was 22.1 months with cemiplimab versus 14.3 months with chemotherapy (HR, 0.68; 95% CI, 0.53-0.87; P = .0022). The median PFS was 6.2 months in the cemiplimab arm versus 5.6 months in the chemotherapy arm (HR, 0.59; 95% CI, 0.49-0.72; P < .0001).

Importantly, all subgroups derived OS and PFS benefit from cemiplimab, with the exception of Asian patients (HR, 1.34; 95% CI, 0.52-3.42). However, the investigators also noted that the number of events in this subgroup was too small to draw a definitive conclusion from.

In the ITT population, the ORR was 36.5% (95% CI, 31.5%-41.8%) in the cemiplimab arm versus 20.6% (95% CI, 16.5%-25.2%) in chemotherapy arm (P <.0001). The median DOR was 21.0 months in the cemiplimab arm versus 6.0 months in the chemotherapy arm.

Patients in the cemiplimab and chemotherapy arms both had a median time to response of 2.1 months.

PFS and OS curves favored cemiplimab, regardless of PD-L1 expression level. Moreover, higher PD-L1 expression was associated with improved PFS and OS to cemiplimab but not chemotherapy.

Regarding HRQoL, patients in the cemiplimab arm experienced a clinically meaningful improvement in Global Health Status/HRQoL, which was defined as at least a 10-point increase from baseline. Grade 3 or greater treatment-emergent adverse events occurred more frequently in the chemotherapy versus cemiplimab arm.

The majority of patients who progressed on chemotherapy (73.9%) received cemiplimab as a crossover treatment. Additionally, 31.6% of patients who progressed on cemiplimab (n = 50) received extended cemiplimab treatment with the addition of chemotherapy.

Notably, cemiplimab-rwlc is the first systemic treatment approved in the United States and European Union for adults with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation.


1. FDA approves Libtayo (cemiplimab-rwlc) monotherapy for patients with first-line advanced non-small cell lung cancer with PD-L1 expression of ≥50%. News release. Regeneron Pharmaceuticals, Inc. February 22, 2021. Accessed February 22, 2021. https://prnmedia.prnewswire.com/news-releases/fda-approves-libtayo-cemiplimab-rwlc-monotherapy-for-patients-with-first-line-advanced-non-small-cell-lung-cancer-with-pd-l1-expression-of-50-301232638.html

2. Agilent PD-L1 IHC 22C3 pharmDx receives expanded FDA approval in non-small cell lung cancer (NSCLC). News release. Agilent Technologies. February 22, 2021. Accessed February 23, 2021. https://www.agilent.com/about/newsroom/presrel/2021/22feb-ca21004.html

3. FDA accepts for priority review Libtayo® (cemiplimab-rwlc) for advanced non-small cell lung cancer with PD-L1 expression of ≥50% [news release]. Regeneron. Published October 29, 2020. Accessed February 5, 2021. https://investor.regeneron.com/news-releases/news-release-details/fda-accepts-priority-review-libtayor-cemiplimab-rwlc-advanced

4. Sezer A, Kilickap S, Gümüş M, et al. EMPOWER-Lung 1: Phase 3 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%.Annals of Oncology. 2020;31(suppl_4):S1142-S1215. doi: 10.1016/annonc/annonc325