Cemiplimab Nears EU Approval for CSCC

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending approval of 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, the manufacturer of the PD-1 inhibitor.

The CHMP recommendation is based on a combined analysis of data from the phase II EMPOWER-CSCC-1 (Study 1540) trial and 2 advanced CSCC expansion cohorts from a phase I trial (Study 1423). The 108-patient combined analysis included 75 patients with metastatic CSCC and 33 patients with locally advanced CSCC.

Across the entire population, the overall response rate (ORR) at a median follow-up of 8.9 months was 47% (95% CI, 38-57). The complete response (CR) rate was 4% and the partial response (PR) rate was 44%. The duration of response ranged from 1 month to over 15 months. Sixty-one percent of patients had a duration of response ≥6 months.

Among 75 patients with metastatic CSCC, the ORR was 47% (95% CI, 35-59). The CR rate was 5% and the PR rate was 41%. The duration of response ranged from 3 months to over 15 months. Sixty percent of patients had a duration of response ≥6 months. In the 33 patients with locally advanced disease, the ORR was 49% (95% CI, 31-67), comprising all PRs. The duration of response ranged from 1 month to 13 months. Sixty-three percent of responders had a duration of response ≥6 months.

The safety population evaluated included 163 patients with metastatic or locally advanced CSCC from Studies 1540 and 1423. The patients received cemiplimab intravenously at 1 mg/kg every 2 weeks (n = 1), 3 mg/kg every 2 weeks (n = 139), or 350 mg every 3 weeks (n = 23). Treatment was administered until unacceptable toxicity, disease progression, or completion of the planned regimen. The median duration of exposure was 20 weeks (range, 3 days to 1.4 years).

The most common adverse events (AEs) across all grades included fatigue (29%), rash (25%), diarrhea (22%), nausea (19%), musculoskeletal pain (17%), pruritus (15%), constipation (12%), and decreased appetite (10%). The most common grade 3/4 AEs included musculoskeletal pain (3%), fatigue (2%), rash (1.2%), diarrhea (0.6%), constipation (0.6%).

Treatment discontinuation associated with AEs occurred in 5% of patients, with the specific AEs being pneumonitis, autoimmune myocarditis, hepatitis, aseptic meningitis, complex regional pain syndrome, cough, and muscular weakness. Additionally, serious AEs occurred in 28% of patients and included cellulitis, sepsis, pneumonia, pneumonitis, and urinary tract infection.

The application for cemiplimab in the EU will now be reviewed by the European Commission for a final decision on approval in the coming months. Regeneron noted in its press release that an approval at this time would be conditional and would require additional confirmatory data regarding cemiplimab’s benefit-risk profile.

According to Regeneron, the incidence of CSCC in Europe is twice that of melanoma. However, there are currently no treatments approved in the EU for advanced CSCC.

FDA prescribing information for Libtayo. Accessed April 29, 2018. https://bit.ly/2V1wrDu.