Background
Phase 1/2, multicenter, open-label EMPOWER-CSCC-1. N=107 advanced cutaneous squamous cell carcinoma (CSCC) in two pivotal cohorts: metastatic (Group 1, n=59) and locally advanced (Group 2, n=48). Cemiplimab (anti-PD-1); no biomarker selection. ECOG PS 0–1; disease not amenable to curative surgery or radiation.
Interventions and follow up
Treatment: Cemiplimab 3 mg/kg IV q2w (initial) or 350 mg IV q3w (expansion) until progression, intolerance, or up to ~96 weeks (single-arm)
Primary endpoint: ORR per RECIST 1.1 by independent central review in each cohort
mFollow up: Median 7.9 months at primary analysis
Primary endpoint: ORR per RECIST 1.1 by independent central review in each cohort
mFollow up: Median 7.9 months at primary analysis
Results
ORR (metastatic, Group 1): 47.2% (28/59; 95% CI 34.0–60.7); 61% ongoing at cutoff
ORR (locally advanced, Group 2): 43.8% (21/48; 95% CI 29.5–59.0); 57% ongoing
mDOR (mCSCC): Not reached at primary analysis
ORR (locally advanced, Group 2): 43.8% (21/48; 95% CI 29.5–59.0); 57% ongoing
mDOR (mCSCC): Not reached at primary analysis
Adverse events
Grade ≥3 TRAE: 45.2% overall
Most common grade ≥3: diarrhea 6.8%, fatigue 5.8%, pneumonitis 4.9%
Discontinuation: 8.8% treatment-related
Immune-mediated: thyroid dysfunction, pneumonitis, colitis (steroid-managed)
Most common grade ≥3: diarrhea 6.8%, fatigue 5.8%, pneumonitis 4.9%
Discontinuation: 8.8% treatment-related
Immune-mediated: thyroid dysfunction, pneumonitis, colitis (steroid-managed)
Conclusions
Cemiplimab achieved ~47% ORR with durable responses in metastatic CSCC and ~44% ORR in locally advanced CSCC — the first effective systemic therapy for this disease. Established cemiplimab as the first FDA-approved systemic treatment and a new standard of care in advanced CSCC.
Key Limitations
Single-arm, nonrandomized; no comparator. ORR surrogate endpoint; short median follow-up (7.9 mo) with immature survival data. Two dosing regimens pooled.
Clinical Context
First FDA-approved (2018) and ESMO-endorsed systemic therapy for advanced CSCC; cemiplimab is preferred first-line for metastatic/locally advanced disease not curable by surgery or radiation.