Interim results of the phase II EMPOWER-CSCC-1 study previously demonstrated promising clinical activity of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC), a patient population facing a poor prognosis. Further follow-up data at approximately 43 months after the primary analysis demonstrate incremental improvements in duration of response with cemiplimab across all advanced CSCC study groups. In addition, trial investigators reported improvements in objective response rate and complete response rate on the cemiplimab 350 mg Q3W regimen without additional safety signals.
Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer with a rising incidence in recent years. Although most cases of CSCC can be cured by complete surgical excision, a small but substantial number of patients subsequently develops either metastatic CSCC (mCSCC) or locally advanced CSCC (laCSCC) that is no longer amenable to curative surgery or curative radiotherapy. Patients with mCSCC and laCSCC, collectively referred to as “advanced CSCC”, face a poor prognosis with a median overall survival (OS) of approximately 15 months with conventional chemotherapy or epidermal growth factor receptor inhibitors. Cemiplimab is a human immunoglobulin G4 monoclonal antibody directed to the programmed cell death (PD)-1 receptor for which previous reports demonstrated clinically meaningful activity in patients with advanced CSCC with a safety profile that is consistent with that of other anti–PD-1 agents. Subsequent updates of this study demonstrated durable responses with the emergence of new objective responses, including complete responses, over time. On the basis of these results, cemiplimab is approved for treatment of patients with advanced CSCC in the US and Europe, and is approved or under review by other health authorities.
EMPOWER-CSCC-1 is an open-label, non-randomised, multicentre, international phase II study including 193 patients with advanced CSCC. Patients were assigned to cemiplimab 3 mg/kg every two weeks (Q2W, Group 1; mCSCC with N= 59, Group 2; laCSCC with N= 78) for up to 96 weeks or cemiplimab 350 mg Q3W (Group 3, N= 56) for up to 54 weeks. Tumour assessments were performed every eight weeks for patients with mCSCC or laCSCC treated with 3 mg/kg Q2W, and every nine weeks for patients with mCSCC treated with the 350 mg Q3W schedule. The primary objective of the trial was to evaluate the objective response rate (ORR) by independent central review (ICR) per Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST 1.1) (for scans) and modified World Health Organisation (WHO) criteria (for photos). During the 2021 World Melanoma Congress – EADO 2021, longer follow-up data of this trial were presented at approximately 43 months after the primary analysis of the first group in this study.
Compared to the previous update, two additional patients achieved a complete response in Group 3 (N=9 after ~1-year follow-up vs. N=11 after 2-year follow-up). The updated ORR by ICR was reported at 47.2% for all patients; 50.8% for Group 1 and 44.9% for Group 2. In Group 3, the ORR increased from 42.9% in the previous update to 46.4% in the current analysis. Clinical activity with cemiplimab by ICR was observed regardless of patient age with an ORR of 42.9% for patients younger than 65 years, 53.0% for patients aged 65-<75 years and 44.9% for patients of at least 75 years old. The median duration of response (DoR) has not been reached. In responding patients, the estimated proportion of ongoing response at 24 months improved incrementally to 72.8% overall as compared to 69.4% at the previous analysis. The ICR Kaplan–Meier estimated progression-free survival at 24 months improved to 46.9%, up from 44.2% in the previous analysis. The median overall survival (OS) was not yet reached, with a 24-month Kaplan–Meier estimated probability of OS of 73.1%.
Overall, the most common treatment-emergent adverse events (TEAEs) of any grade were fatigue (N= 67, 34.7%), diarrhoea (N= 53, 27.5%), and nausea (N= 46, 23.8%). In total, 95 (49.2%) patients experienced at least one Grade ≥3 TEAE. The most common Grade ≥3 TEAEs were hypertension (N= 9; 4.7%), anaemia, cellulitis, and pneumonia (all N= 8; 4.1%). In total, 29 patients (15.0%) experienced at least one Grade ≥3 immune-related adverse event (irAE) by investigator assessment, of which pneumonitis (N= 6, 3.1%) and autoimmune hepatitis (N= 3; 1.6%) were the most common. No new TEAEs resulting in death were reported.
Compared to the previous analysis of this study, the 43-month follow-up data demonstrate incremental improvements in duration of response with cemiplimab treatment across all advanced CSCC study groups, with improvements in the ORR and complete response rate on the cemiplimab 350 mg Q3W regimen. There were no new safety signals compared with previous reports on cemiplimab in advanced CSCC. As such, these updated results further solidify the potential of cemiplimab in this setting.
Rischin D, et al. Phase 2 Study of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Follow-Up at 43 Months. Presented at EADO 2021; Abstract P-236.