On September 28, 2018, the FDA approved programmed death 1 (PD-1) immune-checkpoint inhibitor cemiplimab-rwlc (Libtayo®, Regeneron) for use in patients with metastatic cutaneous squamous cell carcinoma (CSCC) and patients with locally advanced CSCC unamenable for curative surgery or curative radiation.

Studies R2810-ONC-1423 and R2810-ONC-1540

The FDA approval was based on the objective response rates (ORR) with cemiplimab-rwlc in patients with advanced CSCC participating in two clinical trials.

The first study was an open-label, multicentre, dose-finding study (R2810-ONC-1423, NCT02383212) with expansion cohorts which investigated cemiplimab-rwlc in patients with various advanced solid tumours.

The second study was an open-label, multi-centre, non-randomised, multicohort study (R2810-ONC-1540, NCT02760498) which investigated cemiplimab-rwlc metastatic or locally advanced CSCC patients unamenable for surgery or radiation and regardless of prior therapies received.

The ORR (by RECIST 1.1) for patients with metastatic CSCC was assessed by an independent review committee (IRC). Patients with locally advanced CSCC underwent a composite response assessment of clinical response criteria by digital photography and RECIST 1.1.

The two studies included 108 patients with advanced CSCC, including 75 (69%) with metastatic CSCC and 33 (31%) with locally advanced CSCC. The ORR by IRC was 47% (95% CI, 38-57), made up of 4% complete responses (CR) and 44% partial responses (PR).

The ORR for patients with metastatic CSCC was 47% (95% CI, 35-59) and 49% (95% CI, 31-67) for those with locally advanced disease. At the time of data cut-off, the median response duration was not yet reached (range: 1.0 to 15.2+ months), with 61% of the responses lasting six months or longer. The ORR and durability results were consistent across CSCC subtypes. In patients with locally advanced CSCC, clinical observations as per photographic data matched the radiographic responses.

Safety

The safety data included 534 patients treated in both cemiplimab-rwlc trials. Serious adverse reactions included immune-related adverse events (irAEs) such as pneumonitis, hepatitis, colitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus and nephritis as well as infusion reactions.  Common adverse reactions were fatigue, rash and diarrhoea.

Prescribing information Libtayo.