FDA Approves Cemiplimab for CSCC

The FDA has approved the PD-1 inhibitor cemiplimab (Libtayo) 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.

The approval 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, 38-47). 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 over 13 months. Sixty-three percent of patients had a duration of response ≥6 months.

“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,” Richard Pazdur, MD, 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, said in a statement. “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.”

Results from a phase II study presented at the 2018 ASCO Annual Meeting and published in the New England Journal of Medicine showed that cemiplimab induced an ORR of 47.5% in patients with metastatic CSCC.1,2 At a median follow-up of 7.9 months, 28 of 59 patients had a response, including 4 (6.8%) partial responses and 24 (40.7%) complete responses. Among the responders, 57% had responses >6 months, and 82% had an ongoing response and continued to receive the PD-1 inhibitor. Responses were observed irrespective of prior systemic therapy.

The phase II 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 cemiplimab intravenously at 3 mg/kg every 2 weeks. The median age of the 59 patients was 71 (range, 38-93), with 43 (73%) patients aged ≥65 years.

Ninety-two percent of patients were male, 39% had and ECOG performance score of 0 and 61% had a score of 1. The primary site of CSCC included head or neck (64%), arm or leg (20%), and trunk (15%). Forty-four percent of patients were treatment naive, 37% had 1 prior regimen for CSCC, and 19% had ≥2 prior regimens. Three-fourths (76%) of patients had distant metastasis and 24% had regional metastasis only.

The median time to response was 1.9 months (range 1.7-6.0). The median duration of response had not been reached at the data cutoff. Beyond the 47.4% (95% CI, 34-61) ORR, the stable disease rate was 15% (n = 9) and the progressive disease rate was 19% (n = 11). Twelve percent (n = 7) of patients could not be evaluated and 7% (n = 4) had nontarget lesions only. The durable disease control rate (DCR) was 61.0% (95% CI, 47.4-73.5).

The ORR in treatment-naive patients was 57.7% (15/26; 95% CI, 36-9-76.6), including 3 complete responses and 12 partial responses. The durable DCR was 69.2% (95% CI, 48.2-85.7). Among previously treated patients, the ORR was 39.4% (13/33; 95% CI, 22.9-57.9), including 1 CR and 12 PRs. The durable DCR was 54.5% (95% CI, 36.4-71.9).

Grade ≥3 adverse events (AEs) occurred in 42% of patients, leading to treatment discontinuation in 3 patients, and were linked to 3 patient deaths. Grade ≥3 AEs included diarrhea (n = 1), fatigue (n = 1), constipation (n = 1), anemia (n = 1), and pneumonitis (n = 2). Serious AEs occurred in 29% of patients. There were also 8 patient deaths due to disease progression.

The article published in NEJM also included phase I 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 II study. The ORR was 50% (95% CI, 30-70) among these patients, comprising all partial responses (n = 13). Six patients had stable disease, 3 had progressive disease, 3 could not be evaluated, and 1 had nontarget lesions only. The durable DCR was 65% (95% CI, 44-83) and the median time to response was 2.3 months (95% CI, 1.7-7.3).

Based on the phase I and II data, the FDA granted a priority review in April 2018 to a biologics license application (BLA) for cemiplimab for the treatment of patients with metastatic CSCC or patients with locally advanced CSCC who are not eligible for surgery. The FDA is scheduled to make its decision on the BLA by October 28, 2018.

References

Rischin CD, Migden MR, Chang A, et al. Primary analysis of phase 2 results for cemiplimab, a human monoclonal anti-PD-1, in patients with metastatic cutaneous squamous cell carcinoma (mCSCC). J Clin Oncol. 2018;36 (suppl; abstr 9519).

Migden MR, Rischin CD, Schmults A, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma [published online June 4, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1805131.