Cemiplimab Demonstrates Doubled Overall Survival as Monotherapy in First-Line PD-L1-High NSCLC

In recent years, with the continuous advancement of immunotherapy, certain types of cancer have been effectively controlled. The star drug in immunotherapy, PD-1 antibodies, has become a key focus for major pharmaceutical companies striving for breakthroughs. In 2018, based on a Phase I clinical trial (NCT02383212), the U.S. FDA granted Breakthrough Therapy Designation to Regeneron Pharmaceuticals’ PD-1 inhibitor, cemiplimab, for the treatment of metastatic cutaneous squamous cell carcinoma (CSCC) in patients who are not candidates for curative surgery or curative radiation therapy. This marked the first FDA-approved drug specifically indicated for advanced CSCC, garnering significant attention for this novel PD-1 inhibitor. Recently, Regeneron announced that the FDA has accepted its supplemental Biologics License Application (sBLA) for cemiplimab as a first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 ≥50%. Cemiplimab is thus poised to become another immune checkpoint inhibitor approved as monotherapy for patients with high PD-L1 expression, following pembrolizumab (“Keytruda”) and atezolizumab (“Tecentriq”).

This sBLA is based on the open-label, randomized, multicenter Phase III EMPOWER-Lung 1 study. The study enrolled 710 patients with locally advanced Stage IIIB/C non-small cell lung cancer (NSCLC) who were not candidates for surgical resection or definitive chemoradiotherapy, or whose disease progressed after prior chemoradiotherapy, as well as patients with previously untreated metastatic Stage IV NSCLC. All patients had high PD-L1 expression (≥50%). Patients with well-controlled hepatitis B, hepatitis C, or HIV; pre-treated and stable brain metastases; and both squamous and non-squamous NSCLC histologies were eligible for the trial. Patients were randomized in a 1:1 ratio to receive either cemiplimab 350 mg intravenously every three weeks for up to 108 weeks, or investigator’s choice of platinum-based doublet chemotherapy for 4–6 cycles (with or without pemetrexed maintenance therapy). Crossover treatment was permitted for patients in either arm upon significant disease progression.

At the time of the second interim analysis in March 2020, a total of 355 and 342 patients in the overall population had received cemiplimab and chemotherapy, respectively. Among patients in the chemotherapy group who experienced disease progression, 73.9% (150/203) crossed over to receive cemiplimab; among patients in the cemiplimab group who experienced disease progression, 31.6% (50/158) received chemotherapy in addition to cemiplimab.

In the intention-to-treat (ITT) population with PD-L1 ≥50%, 283 and 280 patients received cemiplimab and chemotherapy, respectively. Among them, 88 patients did not undergo PD-L1 testing in accordance with the enrollment criteria before August 2018 but were found to have PD-L1 ≥50% upon retesting; 475 patients underwent PD-L1 testing in accordance with the enrollment criteria after August 2018 and were found to have PD-L1 ≥50%.

In the ITT population, the median follow-up time was 13.1 months in both the cemiplimab and chemotherapy groups. Overall survival (OS) was significantly prolonged in the cemiplimab group (22.1 vs. 14.3 months), with a 32% reduction in the risk of death (HR = 0.68; 95% CI: 0.53–0.87; p = 0.002).

In the ITT population with PD-L1 ≥50%, the median follow-up times for the cemiplimab and chemotherapy groups were 10.8 and 10.2 months, respectively; OS was not reached and 14.2 months, respectively, representing a 43% reduction in the risk of death with cemiplimab (HR = 0.57; 95% CI: 0.42–0.77; p = 0.002).

For secondary endpoints, in the ITT population, PFS was significantly prolonged in the cemiplimab group (6.2 vs. 5.6 months), with a 41% reduction in the risk of disease progression (HR = 0.59; 95% CI: 0.49–0.72; p < 0.001). In the ITT population with PD-L1 ≥ 50%, the median PFS was 8.2 months and 5.7 months, respectively, representing a 46% reduction in the risk of disease progression (HR = 0.54; 95% CI: 0.43–0.68; p < 0.001).

For patients with advanced non-small cell lung cancer (NSCLC) who have PD-L1 expression ≥50% and no driver mutations, monotherapy with PD-1/PD-L1 inhibitors or combination with chemotherapy is the preferred treatment regimen. However, selecting the least toxic yet most effective therapy remains a challenge. Patients with PD-L1 expression ≥50% require additional therapeutic options to improve survival rates and optimize chemotherapy-free regimens.

Cemiplimab is a high-affinity, high-potency human PD-1 inhibitor that functions by targeting the PD-1 pathway (a protein found on human immune cells and certain cancer cells). By blocking this pathway, the drug helps the human immune system combat cancer cells. Data from the EMPOWER-Lung 1 study provide the rationale for cemiplimab as a new first-line monotherapy option for patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50%.

Cemiplimab is currently being co-developed by Regeneron and Sanofi under their global collaboration agreement for the treatment of various types of cancer. The extensive clinical program for Cemiplimab focuses on refractory cancers, including skin cancer, cervical cancer, solid tumors, and hematologic malignancies. We look forward to Cemiplimab delivering further new breakthroughs.

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