Positive Topline Results Announced for Cemiplimab in Advanced CSCC

Topline results from the pivotal phase II EMPOWER-CSCC 1 study showed that the PD-1 inhibitor cemiplimab (REGN2810) induced an overall response rate (ORR) of 46.3% in patients with advanced cutaneous squamous cell carcinoma (CSCC).

The median duration of response (DOR) had not yet been reached at the data cutoff point, and 32 of 38 responses are ongoing. At the time of this analysis, all patients had a minimum follow-up of 6 months. The safety profile in the study was generally consistent with approved anti—PD-1 agents.

Regeneron and Sanofi issued a press release reporting that the results will be submitted as part of a rolling biologics license application (BLA) to the FDA. The companies expect to finish the submission early next year. A rolling BLA submission allows for portions of the regulatory application to be submitted to the FDA as they are completed.

The companies also plan to apply for regulatory approval with the European Medicines Agency in the first quarter of 2018.

CSCC is the second most common and second deadliest type of skin cancer in the United States, behind only melanoma. Advanced CSCC is responsible for 3900 to 8800 deaths annually. The disease most often affects older men and has a good prognosis when caught early. However, advanced CSCC can be difficult to treat and multiple surgeries to remove tumors often leave 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.

“For patients with CSCC who cannot be cured by surgery or radiation, there are no FDA-approved treatment options,” Israel Lowy, MD, PhD, vice president of Global Clinical Development and Head of Translational Science and Clinical Oncology, Regeneron, said in a press release. “This is the largest prospective study ever conducted in this disease, and we are pleased that many patients were able to achieve deep and durable responses with cemiplimab monotherapy. The high and durable response rates seen in this study are particularly notable given that the study enrolled patients regardless of biomarker status.”

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

Patients in the fully-enrolled arm were assigned to 3 mg/kg of cemiplimab every 2 weeks. Enrollment continues in the remaining 2 study arms, 1 involving patients with metastatic CSCC assigned to a 350-mg flat dose of cemiplimab every 3 weeks and 1 involving patients with locally advanced and unresectable CSCC receiving 3 mg/kg cemiplimab every 2 weeks.

The FDA named cemiplimab a breakthrough therapy in September based on preliminary results from 2 expansion cohorts of a phase I study of 26 patients with advanced CSCC. Those findings were first reported at the 2017 ASCO Annual Meeting¹ and will be updated at an oncology conference next year.

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 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).

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.

Data were recently presented at the 2017 ASH Annual Meeting demonstrating activity with cemiplimab in patients with B-lymphoid malignancies.

1. 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).