EPIC-A: Phase II trial of cemiplimab plus standard of care chemotherapy followed by maintenance cemiplimab in locally advanced or metastatic penile carcinoma.

1 Background: Platinum-based combination chemotherapy remains the Standard of Care (SoC) treatment for patients with locally advanced/metastatic penile cancer (la/mPC). Prognosis is poor and treatment options are limited. PDL1 is upregulated in 40–60% of cases making a case for immunotherapy as a treatment option for la/mPC. PD-1 inhibitor cemiplimab is approved for patients with locally advanced or metastatic cutaneous SCC. We evaluated efficacy and safety of cemiplimab in combination with SoC chemotherapy in patients with la/mPC. Methods: EPIC-A is a National Cancer Research Network badged phase II non-randomised multi-centre trial evaluating the efficacy and safety of cemiplimab plus platinum-based chemotherapy as first-line treatment in la/mPC. Patients with la/mPC (Tany,N2-3,M0 or T4,Nany,M0 or M1) not amenable for radical treatment received: cemiplimab 350mg IV D1 every 3 weeks (Q3W) + SoC chemotherapy cisplatin/5FU (PF, 27 patients) or docetaxel, ifosfamide, cisplatin (TIP, 2 patients) for 4 cycles followed by cemiplimab alone 350mg IV Q3W up to a total of 34 cycles. The primary end point was investigator assessed Clinical Benefit Rate (CBR) at 12 weeks using RECIST 1.1. The study was designed as an A’Hern (2001) study α=0.05 + power (1-β)=0.8, assuming 25% meeting the clinical end point is a poor treatment (p0=0.25) and 50% is a good treatment (p1=0.5). Assuming a 10% drop out rate, 29 patients were recruited. Results: 29 patients from 11 UK sites were enrolled from Jan 2022- Dec 2023. Median age was 61 years (range 38-76). 93% were ECOG 0-1 and 7% ECOG 2. 76% had metastatic disease (6 bone 23%, 2 liver 6.9%, 16 lung 55.2%). Median number of cycles was 5 (range 1-34) and median follow-up was 8.3 (IQR 5.5-11.5) months. At 12 weeks CBR was 62.1% (95%CI 44.4%, 79.7%) and Objective Response Rate (ORR) was 51.7% (95%CI 34.4%, 68.6%) with 15 PR and no CR. Benefit was maintained at 21 weeks with CBR 48.3% (95%CI 31.4%, 65.6%) and ORR 44.8% (95%CI 28.4%, 62.4%) with 12 PR and 1 CR. Median Progression Free Survival (PFS) was 6.2 (95%CI 3.7, 8.7) months and Overall Survival (OS) is currently estimated to be 15.5 (95%CI 6.0, 25.0) months. Of the reported adverse events (AEs) of any grade, 23% were related to cemiplimab and 31% to chemotherapy. Safety profile is in keeping with reported data on cisplatin based chemotherapy and immunotherapy. There were 2 grade 5 AEs, neither related to cemiplimab but 1 related to chemotherapy. 7 patients discontinued treatment due to an AE, 4 related to cemiplimab (14%). Conclusions: The EPIC-A Trial demonstrates the efficacy and safety of cemiplimab in combination with platinum-based chemotherapy as a treatment for la/mPC. Investigations into potential biomarkers and Quality of Life analysis is ongoing. These data support cisplatin based combination chemotherapy + cemiplimab as a first line SoC treatment option in this rare cancer. Clinical trial information: 95561634.