The European Commission has granted approval to cemiplimab for the treatment of patients with locally advanced or metastatic non–small cell lung cancer whose tumor cells have at least 50% PD-L1 expression and no EGFR, ALK, or ROS1 aberrations and are ineligible for definitive chemoradiation.
The European Commission has granted approval to cemiplimab (Libtayo) for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) whose tumor cells have at least 50% PD-L1 expression and no EGFR, ALK, or ROS1 aberrations and are ineligible for definitive chemoradiation.1
The regulatory agency also gave the green light to cemiplimab with an indication in locally advanced or metastatic basal cell carcinoma (BCC) in patients who have progressed on or are intolerant to a hedgehog pathway inhibitor.2
The safety profile for cemiplimab in both indications was found to be consistent with prior findings of the checkpoint inhibitor.
The approval in advanced NSCLC is based on findings from the international, phase 3 EMPOWER-Lung 1 trial, in which frontline cemiplimab led to a 32% reduction in the risk of death vs chemotherapy (HR, 0.68; 95% CI, 0.53-0.87; P = .0022).3
"Libtayo has demonstrated a highly significant improvement in overall survival compared to chemotherapy for patients with advanced non–small cell lung cancer with high PD-L1 expression and a variety of challenging-to-treat disease characteristics," said Israel Lowy, MD, PhD, senior vice president, translational and clinical sciences, oncology at Regeneron, which jointly develops cemiplimab with Sanofi. "Beyond the primary analysis, we continue to conduct post-hoc analyses of our phase 3 trial with the goal of informing treatment in this patient population."
The indication in BCC was supported by phase 2 data, in which cemiplimab elicited an objective response rate (ORR) of 32% (95% CI, 22%-43%), which included a 26% partial response (PR) rate and a 6% complete response (CR) rate by independent assessment.4 By independent central review, the ORR with cemiplimab was 31% (95% CI, 21%-42%), which featured a 25% PR rate and a 6% CR rate by investigator assessment.
"Since its launch in Europe just 2 years ago, Libtayo has redefined the standard of care for advanced CSCC and has the potential to do the same in advanced BCC," said Peter C. Adamson, MD, global development head, oncology at Sanofi. "Together with Regeneron, we're committed to addressing gaps in the treatment of advanced forms of non-melanoma skin cancer."
In the multicenter, open-label, EMPOWER-Lung 1 study, single-agent cemiplimab was compared with investigator’s choice of platinum-doublet chemotherapy as a frontline treatment for patients with advanced NSCLC whose tumors expressed PD-L1 in at least 50% of tumor cells.
To be eligible for enrollment, patients needed to be at least 18 years old, have histologically or cytologically confirmed stage IIIB or IIIC or stage IV squamous or nonsquamous NSCLC with a PD-L1 expression of 50% or higher, an ECOG performance status of 0 or 1, acceptable organ and bone marrow function, and least 1 measurable lesion per RECIST v1.1 criteria.
Those who were never smokers; had active or untreated brain metastases; harbored EGFR, ALK, or ROS1 aberrations; had active, known, or suspected autoimmune disease that needed systemic treatment within the last 2 years; had or uncontrolled hepatitis B or C or human immunodeficiency virus were ineligible for enrollment.
Patients were randomized 1:1 to receive either cemiplimab at 350 mg every 3 weeks for up to 108 weeks (n = 283) or 4 to 6 cycles of investigator’s choice of platinum-doublet chemotherapy (n = 280). Progression-free and overall survival (OS) were the co-primary end points; secondary end points included ORR, duration of response (DOR), health-related quality of life, and safety.
The median age in the PD-L1 of 50% or higher population was 63.5 years, and 46.5% of these patients were 65 years of age or older. Most patients were male (85.5%), enrolled in Europe (76.5%), had an ECOG performance status of 1 (73%), and were former smokers (65%); 57% of patients had nonsquamous histology. A total 12% of patients had brain metastases and most (84.5%) had metastatic disease at the time of screening.
Results showed that the median OS was 22 months for cemiplimab (range, 18 months to not evaluable [NE]) and 14 months for chemotherapy (range, 12 to 19 months).
In a prespecified analysis of data from patients whose cancers had PD-L1 expression ≥50% (n = 563), cemiplimab showed a 43% reduction in the risk of death compared with chemotherapy (HR, 0.57; 95% CI, 0.42-0.77; P = .0002).5 Here, the median OS with cemiplimab was not reached (range, 18 months to NE) and was 14 months for chemotherapy (range, 11 to 18 months).
Safety was assessed in 697 patients, with a duration of exposure of 27 weeks (range, 9 days to 115 weeks) for those on cemiplimab and 18 weeks (range, 18 days to 87 weeks) on the chemotherapy arm.
Further safety data showed that serious adverse effects (AEs) that occurred in at least 2% of patients were pneumonia (5% cemiplimab vs 6% chemotherapy) and pneumonitis (2% vs 0%, respectively). AEs that led to treatment discontinuation occurred in 6% of patients on cemiplimab, which included pneumonitis, pneumonia, ischemic stroke, and increased aspartate aminotransferase.
In the ongoing, open-label, multicenter, non-randomized, phase 2 trial, investigators enrolled patients with unresectable locally advanced BCC or metastatic BCC, which comprised nodal or distant metastases. Patients in each of these cohorts had either progressed on a prior hedgehog inhibitor, did not achieve an objective response after 9 months on hedgehog inhibitor therapy, or were intolerant of a prior hedgehog inhibitor. An ECOG performance status of 0 or 1 and at least 1 measurable lesion at baseline were required.
The primary end point was confirmed ORR; DOR via independent central review was a key secondary endpoint.
Patients who had ongoing or recent autoimmune disease that needed systemic immunosuppression, who had previously received anti–PD-1 or PD-L1 therapy or who had a concurrent malignancy other than BCC were not excluded. Patients who had a prior malignancy other than BCC within 3 years of the first dose of cemiplimab, except for tumors with negligible risk of metastasis or death, could not participate.
The median age of patients was 70 years (range, 42-89) and more than half (66.7%) were male. About 60% of patients had an ECOG performance status of 0 and 89.3% had a primary tumor site in the head and neck; 71.4% of patients previously discontinued hedgehog inhibitor therapy due to disease progression. A total 38.1% were intolerant to vismodegib (Erivedge), 4.8% were intolerant to sonidegib (Odomzo), and 8.3% did not have better than stable disease after 9 months on a hedgehog inhibitor.
Additional findings showed that an estimated 90% of patients across both groups had a DOR of 6 months or longer per Kaplan Meier estimates, and the median DOR has not been reached for either group. The median duration of follow-up was 16 months for locally advanced BCC and 9 months for metastatic BCC.
Regarding safety, which was assessed in 816 patients across all 4 single-agent cemiplimab monotherapy trials in its approved indications, data showed that serious AEs occurred in 30% of cemiplimab-treated patients; 8% of these led to discontinuation. Immune-related AEs occurred in 22% of patients; permanent discontinuation happened in 4% of patients, the most common of which included hypothyroidism (8%), hyperthyroidism (3%), pneumonitis (3%), hepatitis (2%), colitis (2%) and immune-related skin AEs (2%).
Cemiplimab previously gained an indication in the European Union as the first treatment for adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or radiation.