Efficacy of cimepilimab combined with chemotherapy in advanced/metastatic penile cancer

Combining first-line cemiplimab (Cemiplimab and standard of care (SOC) platinum-based chemotherapy followed by maintenance cemiplimab may provide clinical benefit for patients with locally advanced or metastatic penile cancer, according to results from the Phase 2 EPIC-A trial (ISRCTN95561634) presented at the 2025 Genitourinary Cancers Symposium.

At 12 weeks, the clinical benefit rate (CBR) of the study treatment was 62.1% (95% CI, 44.4%-79.7%); 0 patients had complete response (CR), 15 patients (51.7%) had partial response (PR), and 3 patients (10.3%) had stable disease (SD). The objective response rate (ORR) at 12 weeks was 51.7% (95% CI, 34.4%-68.6%). At 21 weeks, the CBR was 48.3% (95% CI, 31.4%-65.6%); 1 patient (3.4%) achieved CR, 12 patients (41.4%) experienced PR, and 1 patient had an ORR (3.4%) of SD. The ORR at 21 weeks was 44.8% (95% CI, 28.4%-62.4%). For ORR and CBR, the lower bound of the 95% confidence interval was greater than the 25% null hypothesis limit. The median progression-free survival (PFS) was 6.2 months (95% CI, 3.7-8.7), and the median overall survival (OS) was 15.5 months (95% CI, 6.0-25.0).

The EPIC-A trial provides important data on the efficacy and safety of cimepilimab in combination with platinum-based chemotherapy in patients with locally advanced or metastatic penile cancer. These data support cisplatin-based combination chemotherapy plus cimepilimab as a first-line treatment regimen with the potential to improve outcomes in this rare cancer.

EPIC-A was a nonrandomized, open-label trial that enrolled 29 patients who received 350 mg of intravenous (IV) cimepilimab on the first day of each treatment cycle and 4 cycles of intravenous cisplatin chemotherapy every 3 weeks. Patients can then transition to maintenance therapy with 350 mg of cimepilimab intravenously on Day 1 every 3 weeks for up to 30 cycles. SOC chemotherapy includes 80 mg/m2 cisplatin on day 1 and 4000 mg/m2 fluorouracil on days 1 to 4; or 75 mg/m2 cisplatin, 175 mg/m2 paclitaxel (Abraxane), and 3600 mg/m2 ifosfamide.

Eligible patients had histologically confirmed diseaseTxN3M0, TxN2M0, T2N1M0, T4anyN, or M1 locally advanced or metastatic penile cancer; no prior chemotherapy for penile cancer; ECOG performance status 0 to 2; normal renal, liver, and bone marrow function; measurable disease according to RECIST 1.1 criteria. The median patient age was 61 years (range, 38-76 years); patients had ECOG performance status of 0 (45%), 1 (48%), and 2 (7%); 24% had locally advanced disease and 76% had metastatic disease. Metastatic sites were lung (55.2%), bone (23.0%), and liver (6.9%). Patients received treatment for a median of 5 cycles (range, 1-34), and the median follow-up was 15.0 months (IQR, 6.2-21.6).

The primary trial endpoint is investigator-assessed CBR at 12 weeks. Secondary endpoints include safety; CBR at 1, 2, and 3 years; ORR, PFS, OS, and quality of life. No new safety signals were identified with the combination, and the safety profile was consistent with previously reported drug data.

The most common grade 3 or higher chemotherapy-related adverse effects (AEs) included gastrointestinal (GI) disorders (13.6%), blood and lymphatic system AEs (9.1%), infections and infestations (9.1%), and cardiac disorders ( 4.5%); the most common cimipilimab-related adverse events were infections and infestations (22.2%), gastrointestinal diseases (11.1%), immune system diseases (11.10%) and vascular diseases (11.11%). In addition, 23% of adverse events were related to cimepilimab, and 31% of adverse events were related to chemotherapy. Two grade 5 adverse events occurred; 1 due to chemotherapy and 0 due to cimepilimab. Seven patients discontinued treatment, four of which were related to cimepilimab.

References:https://www.onclive.com/view/cemiplimab-plus-chemotherapy-yields-responses-in-advanced-metastatic-penile-carcinoma