FDA Approves LIBTAYO® for Non Small Cell Lung Cancer with High PD-L1 Expression

SUMMARY: The FDA on February 22, 2021, approved LIBTAYO® (Cemiplimab-rwlc) for the first line treatment of patients with advanced Non Small Cell Lung Cancer (NSCLC) (locally advanced who are not candidates for surgical resection or definitive chemoradiation or metastatic), whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] 50% or more), as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations.

The American Cancer Society estimates that for 2021, about 235,760 new cases of lung cancer will be diagnosed and 131,880 patients will die of the disease. Lung cancer is the leading cause of cancer-related mortality in the United States. Non Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has revolutionized cancer care and has become one of the most effective treatment options, by improving Overall Response Rate and prolongation of survival, across multiple tumor types.

Available Immune Checkpoint Inhibitors (ICIs) target Programmed cell Death protein-1 (PD-1) receptors on T cells, as well as Programmed cell Death Ligand-1 (PD-L1), PD-L2 and Cytotoxic T-Lymphocyte-Associated protein-4 (CTLA-4), and many other important regulators of the immune system, which are upregulated in some tumor types. T-cell proliferation and cytokine production is inhibited upon binding of the PD-1 ligands PD-L1 and PD-L2, to the PD-1 receptor found on T cells.

LIBTAYO® is a recombinant human immunoglobulin G4 (IgG4) monoclonal antibody that binds to PD-1 and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response. Unleashing the T cells results in T cell proliferation, activation and a therapeutic response. LIBTAYO® is indicated for the treatment of subsets of patients with advanced Basal Cell Carcinoma and advanced cutaneous Squamous Cell Carcinoma.

The present FDA approval of LIBTAYO® is based on EMPOWER-Lung 1, which is a multicentre, open-label, global, Phase III trial, which examined the benefit of LIBTAYO® in the first-line treatment of advanced NSCLC with PD-L1 expression of at least 50%. In this study, 710 (N=710) patients (intent-to-treat) with Squamous or non-Squamous, locally advanced NSCLC who were not candidates for surgical resection or definitive chemoradiation, or with metastatic NSCLC were randomized (1:1) to receive LIBTAYO® 350 mg IV every 3 weeks for up to 108 weeks (N=356) or 4-6 cycles of investigator’s choice of platinum doublet chemotherapy (N=354). The most common chemotherapy regimens selected were Carboplatin plus Paclitaxel, Carboplatin plus Pemetrexed, and Carboplatin plus Gemcitabine. Crossover from chemotherapy to LIBTAYO® was allowed following disease progression, and never-smokers were not eligible for the trial. The co-Primary end points of the study were Overall Survival (OS) and Progression Free Survival (PFS), per the Blinded Independent Review Committee. Primary endpoints were assessed in the intention-to-treat population and in a prespecified population of patients with PD-L1 of at least 50%. Secondary end points included Overall Response Rate (ORR), Duration of Response (DOR), Health-Related Quality of Life (HRQoL), and Safety.

This trial demonstrated statistically significant improvements in OS and PFS for patients receiving LIBTAYO® compared to those treated with platinum-based chemotherapy, despite a high crossover rate (74%). The median OS was 22.1 months with LIBTAYO® versus 14.3 months with chemotherapy (HR=0.68; P=0.0022), demonstrating that LIBTAYO® reduced the risk of death by 32% compared to chemotherapy. An additional analysis of 563 patients with proven PD-L1 expression of 50% or higher found that the median OS was Not Reached with LIBTAYO® (N=283) versus 14.2 months with chemotherapy (N=280). LIBTAYO® reduced the risk of death by 43% compared to chemotherapy HR=0.57; P=0.0002). The median PFS was 6.2 months in the LIBTAYO® group and 5.6 months in the chemotherapy group (HR= 0.59; P<0.0001). Among those with PD-L1 expression of 50% or higher, the median PFS was 8.2 months with LIBTAYO® versus 5•7 months with chemotherapy (HR=0•54; P<0•0001). The confirmed ORR was 37% and 21% in the LIBTAYO® and chemotherapy arms respectively, and the median DOR was 21.0 months in the LIBTAYO® arm versus 6.0 months in the chemotherapy arm.

The authors concluded that LIBTAYO® monotherapy significantly improved Overall Survival and Progression Free Survival compared with chemotherapy, in patients with advanced Non Small Cell Lung Cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population.

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Sezer A, Kilickap S, Gümüş M, et al. Lancet. 2021;397:592-604. doi: 10.1016/S0140-6736(21)00228-2.