FDA Grants Priority Review to Cemiplimab for Treatment of Metastatic CSCC

The FDA has fast-tracked the review of cemiplimab, a PD-1 inhibitor, in the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or patients with locally advanced CSCC who are not eligible for surgery. It has granted a priority review to a biologics license application (BLA) for cemiplimab based on data from the phase II EMPOWER-CSCC 1 study (NCT02760498), in which the overall response rate (ORR) was 46.3% in patients with advanced CSCC.

The codevelopers of cemiplimab, Regeneron and Sanofi, also submitted supporting data from 2 phase I expansion cohorts of patients with advanced CSCC. In a statement, they reported that updated data from these phase I and II studies will be presented at the 2018 ASCO Annual Meeting.

Cemiplimab previously received an FDA breakthrough therapy designation in CSCC. The FDA is scheduled to make its decision on the BLA by October 28, 2018.

The ORR data reported from the ongoing, single-arm, open-label EMPOWER-CSCC 1 study were for 82 patients. Approximately two-thirds of the patients had progressed following systemic chemotherapy or radiation.

Patients on the study were divided into 3 cohorts. At the data cutoff, there was 1 fully enrolled cohort, which included patients with metastatic CSCC who received 3 mg/kg of cemiplimab every 2 weeks. The other 2 arms, which are still enrolling, include a group of patients with metastatic CSCC assigned to a 350-mg flat dose of cemiplimab every 3 weeks, and a group with locally advanced and unresectable CSCC receiving 3 mg/kg of cemiplimab every 2 weeks.

At the data cutoff, 32 of 38 responses were ongoing and the median duration of response had not been reached. The minimum follow-up was 6 months. Safety data for cemiplimab were similar to other approved PD-1 inhibitors.

Phase I data for cemiplimab in advanced CSCC were reported at the 2017 ASCO Annual Meeting. The results were for 26 patients enrolled across 2 expansion cohorts of a phase I study. Patients in the expansion cohorts were assigned to 3 mg/kg of cemiplimab every 2 weeks for 48 weeks. Ten patients had metastatic disease and 16 had locally advanced disease.

The investigator-assessed preliminary ORR was 46.2% (95% CI, 26-6-66.6) at the data cutoff date of April 27, 2017. Two patients (7.7%), both with locally advanced disease, had a complete response. Ten patients (38.5%), 6 in the metastatic group and 4 in the locally advanced group, had partial response, including 1 unconfirmed partial complete response. A total of 6 patients (23.1%) had stable disease and 6 others had progressive disease. The disease control rate was 69.2% (95% CI, 48.2-85.7).

Fatigue (23.1%) was the most common (>10%) any-grade treatment-emergent adverse effect (TEAE). Incidence of grade 3 or higher TEAEs was low. Investigators recorded single incidences of arthralgia, maculopapular rash, asthenia, AST elevation, and ALT elevation.

Toxicity led to treatment discontinuation for 2 patients: an 88-year-old woman who developed grade 3 rash after 3 doses and an 86-year-old man who withdrew consent after experiencing grade 3 transaminase elevation and grade 2 fatigue after 6 doses.

Two patients died within 30 days of the final dose, but these were not attributed to cemiplimab.

Papadopoulos KP, Owonikoko TK, Johnson ML, et al. REGN2810: A fully human anti-PD-1 monoclonal antibody, for patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC)—Initial safety and efficacy from expansion cohorts (ECs) of phase I study. J Clin Oncol 35, 2017 (suppl; abstr 9503)