Evaluating Cemiplimab in la/mPC: New Findings From the Phase II EPIC-A Trial

For patients with locally advanced or metastatic penile cancer (la/mPC), platinum-based combination chemotherapy remains the standard of care (SOC), yet treatment options are limited, and prognosis remains poor.

Programmed cell death ligand 1 (PD-L1) is upregulated in 40% to 60% of cases, highlighting the potential for immunotherapy in la/mPC. Cemiplimab, a programmed cell death 1 (PD-1) inhibitor, is currently approved for locally advanced or metastatic cutaneous squamous cell carcinoma. At the American Society of Clinical Oncology 2025 Genitourinary Cancers Symposium, researchers presented efficacy and safety findings from the EPIC-A trial of cemiplimab in combination with SOC chemotherapy for patients with la/mPC.

The phase II EPIC-A trial, conducted by the National Cancer Research Network, is a nonrandomized multicenter trial assessing the safety and efficacy of cemiplimab combined with platinum-based chemotherapy as a first-line treatment for la/mPC.

Patients with la/mPC who were ineligible for radical treatment received 350 mg of intravenous (IV) cemiplimab on day 1 of every three-week cycle, paired with SOC chemotherapy consisting of either cisplatin/5-fluorouracil (27 patients) or docetaxel and ifosfamide with cisplatin (2 patients) for four cycles, followed by 350 mg of IV cemiplimab alone every three weeks for up to 34 cycles.

The primary endpoint was determination of the clinical benefit rate (CBR) at 12 weeks based on RECIST 1.1. The study followed an A’Hern (2001) single-stage design with a significance level (α) of .05 and power (1-β) of .8, defining a CBR of 25% as inadequate (P0=0.25) and a CBR of 50% as promising (P1=0.5). To account for a potential 10% dropout rate, 29 patients were enrolled.

A total of 29 patients from 11 sites across the United Kingdom were enrolled in the trial between January 2022 and December 2023. Ninety-three percent of patients had an Eastern Cooperative Oncology Group (ECOG) classification of 0 or 1, and 7% had an ECOG statusn of 2. Metastatic disease was found in 76% of patients (in the bone, 23%; in the liver, 6.9%; and in the lung, 55,2%),

The median number of cycles was five (range 1–34), with a median follow-up duration of 8.3 months (interquartile range [IQR], 5.5–11.5). At a 12-week assessment, the CBR was 62.1% (95% CI, 44.4%-79.7%), and the objective response rate (ORR) reached 51.7% (95% CI, 34.4%-68.6%), consisting of 15 partial responses (PRs) and no complete responses (CRs).

A sustained benefit was seen at 21 weeks, with a CBR of 48.3% (95% CI, 31.4%-65.6%) and an ORR of 44.8% (95% CI, 28.4%-62.4%) with 12 PRs and 1 CR. The median progression-free survival rate was 6.2 months (95% CI, 3.7-8.7), and the median overall survival rate is currently estimated at 15.5 months (95% CI, 6.0-25.0).

Among reported adverse events (AEs) of any grade, 23% were attributed to cemiplimab and 31% to chemotherapy. The safety profile aligned with existing literature on cisplatin-based chemotherapy and immunotherapy. Two grade 5 AEs occurred. Although neither was related to cemiplimab, one was attributed to chemotherapy. Treatment discontinuation due to AEs occurred in seven patients, with four cases (14%) linked to cemiplimab.

The EPIC-A trial has demonstrated the efficacy and safety of cemiplimab combined with platinum-based chemotherapy as a treatment for la/mPC. Research on potential biomarkers and quality-of-life analysis is ongoing. This new information supports cisplatin-based combination chemotherapy in combination with cemiplimab as a first-line SOC treatment for patients with this rare disease type.