EPIC-A: Phase II Trial of Cemiplimab Plus Standard-of-Care Chemotherapy Followed by Maintenance Cemiplimab in Locally Advanced or Metastatic Penile Carcinoma

Purpose Cisplatin-based combination chemotherapy is standard of care (SoC) for patients with locally advanced/metastatic penile cancer (la/mPC). We evaluated efficacy and safety of cemiplimab plus SoC chemotherapy as first-line treatment in these patients. Methods In this phase II, single-arm, multicenter trial, patients with la/mPC (M 1 ; T any ,N 2-3 ,M 0 ; T 4 ,N any ,M 0 ; T 3 ,N 1 ,M 0 ) not eligible for radical treatment received four cycles of once every 3 weeks cemiplimab 350 mg IV D1 plus SoC chemotherapy: cisplatin/5-fluorouracil (5-FU; 27 patients) or paclitaxel/ifosfamide/cisplatin (two patients), followed by cemiplimab alone, for a maximum of 34 cycles. The primary end point was investigator-assessed clinical benefit rate (CBR) at 12 weeks, evaluated using RECIST 1.1. Results Twenty-nine patients from 11 UK sites were enrolled from January 2022 to December 2023. Median age was 61 years (range, 38-76). 93% had an Eastern Cooperative Oncology Group performance score of 0-1, and 86.2% had metastatic disease (lung 72.5%, bone 32%, and liver 8%). Median cycle number was 5 (range, 1-34) and median follow-up was 15 (IQR, 6.2-24) months. At 12 weeks, CBR was 62.1% (95% CI, 44.4 to 79.7). Median progression-free survival (PFS) and overall survival (OS) were 6.3 (95% CI, 3.7 to 8.7) and 15.7 (95% CI, 6.3 to 20.0) months, respectively. Correlation between p16 status and response was nonsignificant. Adverse events (AEs) of any grade related to cemiplimab or chemotherapy were 20.4% (67/328) and 43.2% (142/328), respectively. AEs ≥ grade 3 were 10.4% (7/67) and 14.8% (21/142), respectively, with two grade-5 AEs, neither related to cemiplimab but one related to chemotherapy. AE-led discontinuation was 34.6% (9/26) and 54.5% (6/11) for cemiplimab and chemotherapy, respectively. Conclusion The EPIC-A trial demonstrates the efficacy and safety profile of cemiplimab in combination with cisplatin-based chemotherapy (5-FU and cisplatin, or paclitaxel, ifosfamide, and cisplatin) as a potential treatment for la/mPC. These data suggest that this combination may be a first-line SoC treatment option in this rare cancer.