Cemiplimab Approved in Europe for Cutaneous Squamous Cell Carcinoma

Axel Hauschild, MD, PhD

The European Commission approved cemiplimab (Libtayo) for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation, according to Regeneron Pharmaceuticals and Sanofi, the manufacturers of the PD-1 inhibitor.

The approval is primarily based on data from the phase II EMPOWER-CSCC-1 trial (Study 1540), which assessed single-agent cemiplimab in 78 patients with locally advanced CSCC and 59 patients with metastatic CSCC. At a median follow-up of 9 months (range, 1 to 28), the objective response rate (ORR) was 44% in the locally advanced group.¹ In the metastatic group, the ORR was 49% at a median follow-up of 17 months.²

"With no other medical treatments approved for advanced CSCC in the EU, Libtayo represents an important new option for patients affected with this advanced skin cancer who cannot be cured by surgery or radiation," Axel Hauschild, MD, PhD, an investigator in the pivotal CSCC clinical program and professor and head of the Interdisciplinary Skin Cancer Center at the University Hospital Schleswig-Holstein in Kiel, Germany, said in a statement. "Results from the Libtayo pivotal trial are very encouraging and demonstrated substantial and durable responses following Libtayo treatment, including in the elderly and regardless of PD-L1 expression levels."

Patients in the EMPOWER-CSCC-1 trial received cemiplimab intravenously at 3 mg/kg every 2 weeks for up to 96 weeks. Patients who had disease progression during follow-up had the option for retreatment. Prior anti—PD-1/PD-L1 therapy was not allowed.

Among the patients with locally advanced disease, the median age was 74 years (range, 45-96), 76% of patients were male, 49% had an ECOG performance status of 0, and 59% had an ECOG performance status of 1. The primary CSCC site was of the head/neck in 79.5% of patients, an extremity in 17.9%, and the trunk in 2.6%. Twelve (15.4%) patients had prior cancer-related systemic therapy and 43 (55.1%) had prior radiotherapy.

In the metastatic CSCC group, the median age was 71 (range, 38-93), 92% were male, 39% had an ECOG performance score of 0, and 61% had an ECOG performance score of 1. The primary CSCC site was head/neck for 64.4%, an extremity for 20.3%, and trunk for 15.3%. Over half (55.9%) of the group had received prior cancer-related systemic therapy and 84.7% had received prior cancer-related radiotherapy.

The complete response (CR) rate was 13% in the locally advanced group, and the partial response (PR) rate was 31%. The median duration of response had not yet been reached, and the median observed time to response was 2 months (range, 2-9). The durable disease control rate was 63% and the median progression-free survival (PFS) and overall survival (OS) were not yet reached.

Among patients with metastatic disease, the CR rate was 17% and the PR rate was 32%. The median duration of response had not yet been reached, and the median observed time to response was 2 months (range, 2-9). As in the locally advanced group, the durable disease control rate was 63% and the median PFS and OS were not yet reached.

The most common adverse events (AEs) in the locally advanced group were fatigue (42%), diarrhea and pruritus (both 27%), nausea (22%), and cough (19%). Ten percent of patients had immune-related AEs of grade ≥3. There was 1 patient death considered to be related to study treatment. In the metastatic CSCC group, the most common AEs were diarrhea (29%), fatigue (25%), and nausea (24%). Grade ≥3 immune-related AEs occurred in 14% of patients.

Cemiplimab was granted conditional marketing authorization, meaning continued approval is contingent on Regeneron and Sanofi supplying additional information to the European Medicines Agency supporting the drug’s benefit-risk profile. To comply, the companies are adding a new patient group to EMPOWER-CSCC-1 to obtain additional data.

In the United States, the FDA approved cemiplimab for patients with CSCC in September 2018.

References

1. Migden MR, Khushalani NI, Chang ALS, et al. Primary analysis of phase 2 results of cemiplimab, a human monoclonal anti—PD-1, in patients (pts) with locally advanced cutaneous squamous cell carcinoma (laCSCC). J Clin Oncol. 2019;37(suppl 15;abstr 6015).
2. Guminski AD, Lim AML, Khushalani NI, et al. Phase 2 study of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with metastatic cutaneous squamous cell carcinoma (mCSCC; Group 1): 12-month follow-up. J Clin Oncol. 2019;37(suppl 15;abstr 9526).