FDA Grants Cemiplimab Breakthrough Designation for CSCC

Kyriakos P. Papadopoulos, MD

The FDA has granted a breakthrough therapy designation to cemiplimab (REGN2810) for the treatment of adults with metastatic cutaneous squamous cell carcinoma (CSCC) and adults with locally advanced and unresectable CSCC, according to Regeneron Pharmaceuticals, the manufacturer of the anti—PD-1 monoclonal antibody.

The breakthrough therapy designation accelerates the development and review of drugs targeting serious or life-threatening conditions. Drugs qualifying for this designation must show credible evidence of a substantial improvement on a clinically significant endpoint over available therapies, or over placebo if there is no available therapy.

CSCC is the second most common and second deadliest type of skin cancer in the United States, behind only melanoma. The disease most often affects older men and has a good prognosis when caught early, but advanced CSCC can be difficult to treat, and multiple surgeries to remove tumors often leaves patients with significant scarring. Surgery has a cure rate of greater than 95% in early stage disease, but there is no standard of care systemic therapy for advanced disease.

“Conventional cytotoxic agents, including cisplatin-based regimens, do obtain responses but are poorly tolerated in this elderly population,” said Kyriakos P. Papadopoulos, MD, a senior clinical investigator with South Texas Accelerated Research Therapeutics in San Antonio. “In a contemporary era, the largest prospective study with targeted agent in a chemo-naïve population with advanced disease showed an overall survival of 8.1 months.”

Papadopoulos presented preliminary results from 2 expansion cohorts of a phase I study involving 26 patients with advanced CSCC at the 2017 ASCO Annual Meeting. Regneron submitted data from this study to the FDA in support of cemiplimab.

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.

At the data cutoff date of April 27, 2017, the investigator assessed preliminary overall response rate (ORR) was 46.2% (95% CI, 26-6-66.6). 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 (DCR) was 69.2% (95% CI, 48.2-85.7).

“Of the 11 patients with confirmed responses, 10 continue to have response at 2 to 10 months and ongoing,” Papadopoulos said. He added that cemiplimab induced rapid, deep, and durable reductions in target lesions.

The drug was active across all PD-L1 expressions. More than 80% of patients were positive for PD-L1 expression (≥1%), but Papadopoulos said there was no apparent association between PD-L1 status and objective response. He added that the numbers are small and should be taken with caution.

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

Two patients discontinued treatment for toxicity: 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. Papadopoulos said the female patient is still receiving posttreatment follow-up.

There were 2 deaths within 30 days of final dose, but Papadopoulos said those were not attributed to cemiplimab.

Investigators are currently recruiting patients with metastatic CSCC and locally advanced and unresectable CSCC for EMPOWER-CSCC 1, a phase II, single-arm, open-label clinical trial of cemiplimab. Regeneron and its global partner Sanofi hope to submit a biologics license application to the FDA based on data from that trial early next year.

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).