FDA Approves Libtayo for Cutaneous Squamous Cell Carcinoma

The FDA has approved the PD-1 inhibitor Libtayo (cemiplimab) for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or patients with locally advanced CSCC who are not candidates for curative surgery or curative radiation.

“We’re continuing to see a shift in oncology toward identifying and developing drugs aimed at a specific molecular target. With the Libtayo approval, the FDA has approved six immune checkpoint inhibitors targeting the the PD-1 / PD-L1 pathway for treating a variety of tumors, from bladder to head and neck cancer, and now advanced CSCC,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This type of cancer can be difficult to treat effectively when it is advanced and it is important that we continue to bring new treatment options to patients.”

The approval is based on a combined analysis of data from the phase 2 EMPOWER-CSCC-1 (Study 1540) trial and 2 advanced CSCC expansion cohorts from a phase 1 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 percent. The complete response (CR) rate was 4 percent and the partial response (PR) rate was 44 percent. The duration of response ranged from one month to over 15 months. Sixty-one percent of patients had a duration of response six or more months.

Among 75 patients with metastatic CSCC, the ORR was 47 percent. The CR rate was 5 percent and the PR rate was 41 percent. The duration of response ranged from three months to over 15 months. Sixty percent of patients had a duration of response of at least six months. In the 33 patients with locally advanced disease, the ORR was 49 percent, comprising all PRs. The duration of response ranged from one month to over 13 months. Sixty-three percent of patients had a duration of response six or more months.

At a median follow-up of 7.9 months, 28 of 59 patients had a response, including 4 (6.8 percent) partial responses and 24 (40.7 percent) complete responses. Among the responders, 57 percent had responses six months or longer, and 82 percent had an ongoing response and continued to receive the PD-1 inhibitor. Responses were observed irrespective of prior systemic therapy.

The phase 2 trial included patients with either metastatic or locally advanced CSCC. The data presented at ASCO were only for the cohort of 59 patients with metastatic disease. These patients received Libtayo intravenously at 3 mg/kg every two weeks. The median age of the 59 patients was 71 (range, 38-93), with 43 (73 percent) patients aged 65 years or older.

Ninety-two percent of patients were male, 39 percent had and ECOG performance score of 0 and 61 percent had a score of 1. The primary site of CSCC included head or neck (64 percent), arm or leg (20 percent), and trunk (15 percent). Forty-four percent of patients were treatment naive, 37 percent had 1 prior regimen for CSCC, and 19 percent had two or more prior regimens. Three-fourths (76 percent) of patients had distant metastasis and 24 percent had regional metastasis only.

The median time to response was 1.9 months. The median duration of response had not been reached at the data cutoff. Beyond the 47.4 percent ORR, the stable disease rate was 15 percent (nine patients) and the progressive disease rate was 19 percent (11 patients). Twelve percent (seven patients) of patients could not be evaluated and 7 percent (four patients) had nontarget lesions only. The durable disease control rate (DCR) was 61.0 percent.

The ORR in treatment-naive patients was 57.7 percent, including three complete responses and 12 partial responses. The durable DCR was 69.2 percent. Among previously treated patients, the ORR was 39.4 percent, including 1 CR and 12 PRs. The durable DCR was 54.5 percent.

Grade 3 or higher adverse events (AEs) occurred in 42 percent of patients, leading to treatment discontinuation in three patients, and were linked to three patient deaths. Grade 3 or higher AEs included diarrhea (one patient), fatigue (one patient), constipation (one patient), anemia (one patient) and pneumonitis (one patient). Serious AEs occurred in 29 percent of patients. There were also eight patient deaths due to disease progression.

The article published in NEJM also included phase 1 study data from expansion cohorts of patients with locally advanced or metastatic CSCC. The findings were for 26 patients treated with the same cemiplimab dose as in the phase 2 study. The ORR was 50 percent among these patients, comprising all partial responses (13 patients). Six patients had stable disease, three had progressive disease, three could not be evaluated and one had nontarget lesions only. The durable DCR was 65 percent and the median time to response was 2.3.