Cemiplimab-rwlc for NSCLC With High PD-L1 approved by FDA

From the ASCO Post

On February 22, 2021, cemiplimab-rwlc was approved for 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 therapy or metastatic) whose tumors have high PD-L1 expression (tumor proportion score ≥ 50%) as determined by a U.S Food and Drug Administration (FDA)-approved test, with no EGFRALK, or ROS1 aberrations.1,2

Supporting Efficacy Data for Cemiplimab-rwlc

Approval was supported by findings from the open-label, phase III Study 1624 (EMPOWER-Lung 1; ClinicalTrials.gov identifier NCT03088540).2,3 In the trial, 710 patients with locally advanced NSCLC who were not candidates for surgical resection or definitive chemoradiation therapy or with metastatic NSCLC were randomly assigned to receive cemiplimab at 350 mg intravenously (IV) every 3 weeks for up to 108 weeks (n = 356) or the investigator’s choice of platinum-based chemotherapy for four to six cycles (n = 354). Chemotherapy regimens consisted of paclitaxel plus cisplatin or carboplatin, gemcitabine plus cisplatin or carboplatin, or pemetrexed plus cisplatin or carboplatin followed by optional pemetrexed maintenance. The main efficacy outcome measures were overall survival and progression-free survival on blinded independent central review.

Patients in the cemiplimab group who experienced disease progression were permitted to continue treatment with the study drug with the addition of four cycles of histology-specific chemotherapy until further disease progression was observed. Of the 203 patients randomly assigned to receive chemotherapy who had disease progression, 150 (74%) crossed over to treatment with cemiplimab.

Median overall survival was 22.1 months (95% confidence interval [CI] = 17.7 months to not estimable) in the cemiplimab group vs 14.3 months (95% CI = 11.7–19.2 months) in the chemotherapy group (hazard ratio [HR] = 0.68, 95% CI = 0.53–0.87, = .0022). Median progression-free survival was 6.2 months (95% CI = 4.5–8.3 months) in the cemiplimab group vs 5.6 months (95% CI = 4.5–6.1 months) in the chemotherapy group (HR = 0.59, 95% CI = 0.49–0.72, < .0001). Objective response rates on blinded independent central review were 37% vs 21%, with median response durations of 21 months (range = 1.9+ to 23.3+ months) vs 6 months (range = 1.3+ to 16.5+ months).

How Cemiplimab-rwlc Works

Cemiplimab is a recombinant human immunoglobulin G4 PD-1–blocking monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway–mediated inhibition of the immune response, including antitumor immune response. In syngeneic mouse tumor models, blocking of PD-1 activity resulted in decreased tumor growth.

Binding of the PD-1 ligands PD-L1 and PD-L2 to PD-1 receptors found on T cells inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors.

How Cemiplimab-rwlc Is Used

Patients with locally advanced or metastatic NSCLC must be selected for treatment based on PD-L1 expression on tumor cells as determined by an FDA-approved test.

The recommended cemiplimab dose for treatment of NSCLC is 350 mg via 30-minute IV infusion every 3 weeks until disease progression or unacceptable toxicity. No dose reduction is recommended. In general, treatment should be withheld for severe (grade 3) immune-mediated adverse reactions and permanently discontinued for life-threatening (grade 4) immune-mediated adverse reactions, recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce the corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.

Infusion should be interrupted or slowed for grade 1 or 2 infusion-related reactions, and treatment should be permanently discontinued for grade 3 or 4 reactions. Prescribing information provides instructions on management of immune-mediated adverse events, including pneumonitis, colitis, hepatitis with no tumor involvement of the liver, hepatitis with tumor involvement of the liver, endocrinopathies, nephritis with renal dysfunction, exfoliative dermatologic conditions, myocarditis, and neurologic toxicities.

Safety Profile

In Study 1624, 54% of patients were exposed to cemiplimab for at least 6 months and 22% for at least 12 months. The most common adverse events of any grade (≥ 10%) in patients receiving the agent were musculoskeletal pain (26% vs 27% in chemotherapy group), rash (15% vs 6%), anemia (15% vs 50%), fatigue (14% vs 26%), decreased appetite (12% vs 18%), pneumonia (11% vs 12%), and cough (11% vs 8%). 

Serious adverse events occurred in 28% of patients in the cemiplimab group, with those occurring in at least 2% being pneumonia and pneumonitis. Adverse events led to treatment discontinuation in 6% of patients, with causes in at least two patients consisting of pneumonitis, pneumonia, ischemic stroke, and increased aspartate aminotransferase.

Cemiplimab has warnings/precautions for immune-mediated adverse reactions, including severe and fatal reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation (HSCT), and embryofetal toxicity.

Immune-mediated adverse reactions can occur in any organ system or tissue and include immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, dermatologic adverse reactions, nephritis and renal dysfunction, and solid organ transplant rejection. Patients should be monitored for early identification and management of such reactions, including evaluation of liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1– or PD-L1–blocking antibody. Patients should be advised not to breastfeed while receiving cemiplimab. 


  • Cemiplimab was approved for first-line treatment of patients with NSCLC whose tumors have high PD-L1 expression as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations.
  • The recommended cemiplimab dose for treatment of NSCLC is 350 mg via 30-minute IV infusion every 3 weeks until disease progression or unacceptable toxicity.


1. U.S. Food and Drug Administration: FDA approves cemiplimab-rwlc for non-small cell lung cancer with high PD-L1 expression. Available at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-cemiplimab-rwlc-non-small-cell-lung-cancer-high-pd-l1-expression. Accessed March 15, 2021.

2. Libtayo (cemiplimab-rwlc) injection, for intravenous use, prescribing informationRegeneron Pharmaceuticals, Inc/sanofi-aventis U.S. LLC, February 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761097s007lbl.pdf. Accessed March 15, 2021.

3. Sezer A, Kilickap S, Gümüş M, et al: 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. Lancet 397:592-604, 2021.