FDA Approves Cemiplimab-rwlc Plus Platinum-based Chemotherapy for Advanced NSCLC

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The FDA has approved cemiplimab-rwlc (Libtayo) in combination with platinum-based chemotherapy in adult patients with advanced non–small cell lung cancer with no EGFR, ALK, or ROS1 aberrations.

The FDA has approved cemiplimab-rwlc (Libtayo) in combination with platinum-based chemotherapy in adult patients with advanced non–small cell lung cancer with no EGFR, ALK, or ROS1 aberrations.

The regulatory decision was supported by findings from a phase 3 trial, referred to as Study 16113 (NCT03409614). The randomized, multicenter, double-blind, active-controlled trial enrolled a total of 466 patients with locally advanced NSCLC who were not eligible to undergo surgical resection or to received definitive chemoradiation, or those with metastatic disease who did not receive prior systemic treatment.

Notably, patients could enroll irrespective of PD-L1 expression status. However, those whose tumors harbored EGFR, ALK, or ROS1 aberrations; who had a medical condition that required systemic immunosuppression; or who had ongoing or recent autoimmune disease in need of systemic treatment, were excluded from the research.

Study participants were randomly assigned 2:1 to receive intravenous (IV) cemiplimab at 350 mg every 3 weeks for the duration of 108 weeks in combination with platinum-based chemotherapy given every 3 weeks for 4 cycles (n = 312), or IV placebo plus chemotherapy (n = 154) .

Chemotherapy consisted of any of the following combinations:

  • Carboplatin area under the curve (AUC) of 5 or 6 plus paclitaxel at 200 mg/m2
  • Cisplatin at 75 mg/m2 plus paclitaxel at 200 mg/m2
  • Carboplatin AUC of 5 or 6 plus pemetrexed at 500 mg/m2
  • Cisplatin at 75 mg/m2 and pemetrexed at 500 mg/m2

Maintenance treatment with pemetrexed was required for thos with nonsquamous disease who received a pemetrexed-based regimen in the first 4 treatment cycles. Treatment continued until disease progression by RECIST v1.1 criteria, intolerable toxicity, or 108 weeks.

Patients were stratified by histology (nonsquamous vs squamous) and PD-L1 expression (<1% vs 1% to 49% vs ≥50%).

The patients had a median age of 63 years (range, 25-84), with 40% of patients at least 65 years of age. Moreover, the majority of patients (84%) were male. Eighty-seven percent of patients were White and 13% were Asian. In terms of ECOG performance status, 15% had a status of 0 and 84% had a status of 1.

Additionally, 85% of patients had metastatic disease and 15% had stage IIIB or IIIC disease and were not eligible for resection or definitive chemoradiation by investigator assessment. In terms of histology, 57% had nonsquamous disease and 43% had squamous disease. Further, 7% of patients had a history of treated brain metastases.

The main efficacy outcome measure was overall survival (OS), and additional measures of interest were progression-free survival (PFS) and overall response rate (ORR) per blinded independent central review (BICR) assessment.

Data showed that the combination resulted in a statistically significant improvement in OS vs chemotherapy alone. The median OS in the investigative arm was 21.9 months (95% CI, 15.5-not evaluable) vs 13.0 months (95% CI, 11.9-16.1) in the placebo arm, translating to a 29% reduction in the risk of death (HR, 0.71; 95% CI, 0.53-0.93; 2-sided P = .0140).

The median PFS with cemiplimab plus chemotherapy was 8.2 months (95% CI, 6.4-9.3) by blinded independent central review (BICR) vs 5.0 months (95% CI, 4.3-6.2) with chemotherapy alone, translating to a 44% reduction in the risk of disease progression or death (HR, 0.56; 95% CI, 0.44-0.70; P <.0001).

Moreover, cemiplimab plus chemotherapy elicited a confirmed ORR of 43% (95% CI, 38%-49%) vs 23% (95% CI, 16%-30%) with chemotherapy alone. The median duration of response was 15.6 months (range, 1.7 to 18.7+) with cemiplimab plus chemotherapy vs 7.3 months (range, 1.8 to 18.8+) with chemotherapy alone.

The safety of the combination was examined in 475 patients with locally advanced or metastatic NSCLC enrolled to the trial. Of those who received cemiplimab, 70% were exposed to the agent for at least 6 months; 35% were exposed for more than 12 months.

In the safety population, the median age was 63 years (range, 25-82), and 41% were at least 65 years of age. Most of the patients were male (86%), White (86%), had metastatic disease (86%), and an ECOG performance status of 1 (83%).

Twenty-five percent of patients experienced serious toxicities, the most common of which included pneumonia, anemia, and neutropenia. Fatal reactions were reported in 6% of patients who received cemiplimab plus chemotherapy and these reactions included death not otherwise specified (2.9%), sudden death (1.0%), acute hepatitis (0.3%), acute respiratory distress syndrome (0.3%), mesenteric artery thrombosis (0.3%), pneumonia (0.3%), pneumonitis (0.3%), and pulmonary hemorrhage (0.3%).

The most common toxicities experienced by at least 15% of patients included alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite. The most common laboratory abnormalities that were grade 3 or 4 in severity comprised anemia, neutropenia, lymphopenia, leukopenia, hyponatremia, thrombocytopenia, hyperglycemia, hypophosphatemia, increased alanine aminotransferase (ALT), hypocalcemia, hyperkalemia, hypermagnesemia, hypokalemia, and increased creatinine.

Thirty-three percent of patients required a dose interruption of cemiplimab because of adverse effects. Reactions that required interruptions in at least 2% of participants included anemia, pneumonia, neutropenia, thrombocytopenia, fatigue, COVID-19 infection, and pyrexia.

Toxicities that led to permanent discontinuation of treatment in at least 2 patients included increased ALT and anemia.


  1. FDA approves cemiplimab-rwlc in combination with platinum-based chemotherapy for non-small cell lung cancer. News release. FDA. November 8, 2022. Accessed November 8, 2022.
  2. Libtayo. Prescribing information. Regeneron Pharmaceuticals, Inc.; 2022. Accessed November 8, 2022.