Cemiplimab Granted Positive EU Opinion for Advanced NSCLC and Basal Cell Carcinoma


The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of cemiplimab for use in 2 advanced cancers: non–small cell lung cancer and basal cell carcinoma.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of cemiplimab (Libtayo) for use in 2 advanced cancers: non–small cell lung cancer (NSCLC) and basal cell carcinoma (BCC).1

Specifically, the monoclonal antibody is recommended for the treatment of adult patients with NSCLC who have a PD-L1 tumor cell expression of greater than 50% and do not harbor EGFR, ALK, or ROS1 aberrations; notably, these patients need to have metastatic or locally advanced disease and not be eligible for definitive chemoradiation. The agent is also recommended for use in adult patients with locally advanced or metastatic BCC who have progressed on, or are intolerant to, a hedgehog pathway inhibitor (HHI).

The positive opinion for the NSCLC indication is based on findings from the phase 3 EMPOWER-Lung 1 trial (NCT03088540), which showed that single-agent cemiplimab significantly improved overall survival (OS) and progression-free survival (PFS) vs chemotherapy in patients with advanced disease and a PD-L1 expression of at least 50%.2

Among the 563 patients with a PD-L1 expression of at least 50%, the median OS had not yet been reached (95% CI, 17.9–not evaluable [NE]) with cemiplimab vs 14.2 months (95% CI, 11.2-17.5) with chemotherapy (HR, 0.57; 95% CI, 0.42-0.77; P = .0002). Moreover, the median PFS was 8.2 months (95% CI, 6.1-8.8) and 5.7 months (95% CI, 4.5-6.2) in the investigative and control arms, respectively (HR, 0.54; 95% CI, 0.43-0.68; P <.0001).

In the multicenter, open-label, global, phase 3 trial, investigators set out to examine single-agent cemiplimab vs 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 of age, 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, and an ECOG performance status of 0 or 1. Patients also needed to have acceptable organ and bone marrow function and least 1 measurable lesion per RECIST v1.1 criteria.

If patients were never smokers; had active or untreated brain metastases; had tumors with EGFR, ALK, or ROS1 aberrations; active, known, or suspected autoimmune disease that needed systemic treatment within the prior 2 years; or uncontrolled hepatitis B or C or human immunodeficiency virus, they were excluded.

Patients were randomized 1:1 to receive either single-agent 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). The co-primary end points of the trial were OS and PFS, while secondary end points included objective response rate (ORR), duration of response (DOR), health-related quality of life (HRQoL), and safety. Investigators also examined pharmacokinetic and immunogenicity, as well as conducted exposure–response analyses.

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. Moreover, most of the patients were male (85.5%), enrolled in Europe (76.5%), had an ECOG performance status of 1 (73%), and were past smokers (65%). Fifty-seven percent of patients had nonsquamous histology, while the rest had squamous histology. Twelve percent had brain metastases and most (84.5%) had metastatic disease at the time of screening.

Additional data in this subgroup revealed that the ORR per independent review committee assessment was 39% (95% CI, 34%-45%) with cemiplimab vs 20% (95% CI, 16%-26%) with chemotherapy. The median DOR in the investigative and control arms was 16.7 months and 6.0 months, respectively.

Among the full intention-to-treat population (n = 710), the median OS with cemiplimab was 22.1 months (95% CI, 17.7-NE) vs 14.3 months (95% CI, 11.7-19.2) with chemotherapy (HR, 0.68; 95% CI, 0.53-0.87; P = .0022). The median PFS in the investigative and control arms was 6.2 months (95% CI, 4.5-8.3) and 5.6 months (95% CI, 4.5-6.1), respectively (HR, 0.59; 95% CI, 0.49-0.72; P <.0001).

Early and sustained clinically meaningful improvements in HRQoL was reported with cemiplimab, but not with chemotherapy.

Regarding safety, 57% of those given cemiplimab and 89% of those who received chemotherapy experienced treatment-related adverse effects (TRAEs); these effects were grade 3 or 4 in 12% and 37% of patients, respectively. The most frequently reported grade 3 or 4 AEs associated with cemiplimab were increased aspartate aminotransferase (1%) and pneumonia (1%). Ten percent vs 9% of patients in the investigative and control arms, respectively, experienced treatment-emergent toxicities that resulted in death.

Three percent of these cases were determined to be associated with cemiplimab; these patients experienced autoimmune myocarditis, cardiac failure, cardiopulmonary failure, cardiorespiratory arrest, nephritis, respiratory failure, septic shock, tumor hyperprogression, and an unknown cause (n = 1, each).

The recommendation for the BCC indication was based on data from a phase 2 trial (NCT03132636), which showed that cemiplimab demonstrated clinical benefit in patients with locally advanced BCC who progressed on an HHI.3 At a median follow-up of 15 months, cemiplimab elicited an ORR of 31% (95% CI, 21.3%-42.0%) per independent central review (ICR) in this patient population; this included a 6.0% complete response (CR) rate and a 25.0% partial response rate.

The phase 2 trial was comprised of 2 cohorts: adult patients with metastatic (nodal and distant) BCC and adult patients with locally advanced BCC. Data from the second cohort were presented during the 2020 ESMO Virtual Congress. Here, a total of 84 patients with locally advanced BCC received 350 mg of intravenous cemiplimab every 3 weeks for up to 93 weeks or until progressive disease.

Investigators conducted tumor assessments in cycles 1 through 5 every 9 weeks and then every 12 weeks for cycles 6 through 9. Tumor response assessments per ICR were done per RECIST v1.1 criteria and/or modified World Health Organization criteria.

To be eligible for participation, patients needed to have a histologically confirmed diagnosis of invasive BCC, have previously progressed or been intolerant to hedgehog inhibition, or had no better state than stable disease (SD) following 9 months of treatment with a hedgehog inhibitor. Patients were also required to have an ECOG performance status of 0 or 1 and at least 1 measurable lesion at baseline.

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 previous 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 study participants 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. Moreover, 71.4% of patients previously discontinued treatment with a hedgehog inhibitor because of disease progression; 38.1% were intolerant to vismodegib (Erivedge), 4.8% were intolerant to sonidegib (Odomzo), and 8.3% did not have better than SD after 9 months on an HHI.

The primary end point of the trial was ORR per ICR, while secondary end points comprised safety and tolerability, DOR, PFS, OS, and CR per ICR.

At a median follow-up of 15 months (range, 0.5-25), additional data showed that 48.8% (n = 41) of patients had SD, 10.7% (n = 9) had progressive disease (PD), and 9.5% (n = 8) were not found to be evaluable. Moreover, the median Kaplan Meier–estimated DOR per ICR had not yet been reached. However, the estimated probability of DOR was 90.9% (95% CI, 68.3%-97.6%) at 6 months; at 12 months, this rate was 85.2% (95% CI, 60.5%-95.0%).

The estimated median PFS was 19.3 months (95% CI, 8.6–not estimable [NE]) with cemiplimab and the estimated 12-month event-free probability was 56.5% (95% CI, 44.3%-67.0%). The estimated median OS was not reached (95% CI, NE–NE) and the estimated 12-month probability of survival was 92.3% (95% CI, 83.6%-96.5%).

Overall responses were noted, irrespective of PD-L1 expression levels. For patients with evaluable PD-L1 that was less than 1% (n = 35), the ORR with cemiplimab was 26% (95% CI, 13%-43%); this included 2 CRs, 7 PRs, and 18 SD cases. Moreover, 5 patients had PD and 3 patients were NE. In those with evaluable PD-L1 status that was 1% or higher (n = 15), the ORR with the agent was 27% (95% CI, 8%-55%); this included 2 CRs, 2 PRs, and 9 SD cases. Here, 1 patient had PD and 1 was NE. In patients who had no evaluable PD-L1 expression status (n = 34), the ORR with cemiplimab was 38% (95% CI, 22%-56%); this included 1 CR and 12 PRs. Fourteen patients had SD, 3 had PD, and 4 were unevaluable.

Additionally, the disease control rates (DCRs) in patients with a PD-L1 expression of less than 1%, 1% or higher, or no evaluable PD-L1 expression were 77%, 87%, and 79%, respectively. Moreover, the durable DCRs were 51%, 53%, and 71%, respectively.

The most frequently reported, any-grade treatment-emergent adverse effects (TEAEs) included fatigue (30%), diarrhea (24%), pruritus (21%), and asthenia (20%). Grade 3 or higher TEAEs included hypertension (5%), fatigue (4%), urinary tract infection (4%), and asthenia, anemia, decreased appetite, headache, and nausea (n = 1 each).


  1. Libtayo (cemiplimab) receives positive CHMP opinion for the treatment in Europe of two advanced cancers. News release. Regeneron Pharmaceuticals, Inc. May 24, 2021. Accessed May 24, 2021. https://prn.to/2QSPSha
  2. Sezer A, Kilickap S, Gümüs 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. 2021;397(10274):592-604. doi:10.1016/S0140-6736(21)00228-2
  3. Stratigos AJ, Sekulic A, Peris K, et al. Primary analysis of phase 2 results for cemiplimab in patients with locally advanced basal cell carcinoma (laBCC) who progress on or are intolerant to hedgehog inhibitors (HHIs). Ann Oncol. 1010; 2020;31(suppl 4):S1175-S1176. doi:10.1016/j.annonc.2020.08.2277
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