EPIC-B: Phase II trial of cemiplimab as first-line treatment in advanced penile carcinoma.

9 Background: Patients with locally advanced or metastatic penile squamous cell carcinoma (la/mPC) have a poor prognosis with very limited therapeutic treatment options. Standard of Care (SoC) treatment remains platinum-based combination chemotherapy with modest outcomes. Some patients are ineligible for chemotherapy and have very limited options for management. PDL1 is upregulated in 40–60% of PC, making a case for immunotherapy as a treatment for la/mPC. We describe the results from the EPIC-B trial, evaluating the efficacy and safety of cemiplimab as first line treatment in la/mPC. Methods: EPIC-B is a National Cancer Research Network badged single arm, multi-center phase II trial, in treatment naïve la/mPC. Patients received cemiplimab 350mg IV D1 every 3 weeks (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 5% meeting the primary end point is a poor treatment (p0=0.05) and 25% is a good treatment (p1=0.25). Assuming a 10% drop out rate, 18 patients were recruited to test this hypothesis. Results: From November 2021, 18 patients from 11 UK sites were enrolled onto EPIC-B over 29 months. Median age was 72 years (range 44-88). Patients with ECOG 0-2 were allowed onto the trial, the majority having ECOG 1 or 2 (0=5%, 1=56% and 2=39%). 83% had metastatic disease (1 bone 5.6%, 1 liver 5.6%, 6 lung 33.3%). Median number of cycles was 4 (range 1-32) and median follow-up was 5.5 (IQR 2.3-8.1) months. At 12 weeks CBR was 38.9% (95%CI 20.3%, 61.4%) and Objective Response Rate (ORR) was 16.6% (95%CI 5.8%, 39.2%) with 3 partial response (PR) and 4 stable disease (SD). Over the full course of treatment 27.7% of patients showed a response to treatment including 1 complete response (1 CR, 4 PR) and 4 patients had SD as their best response. Median Progression Free Survival (PFS) was calculated to be 2.3 (95%CI 1.0, 3.8) months and median Overall Survival (OS) is currently estimated at 6.8 (95%CI 3.7, 9.8) months. For adverse events (AEs) of any grade, 31% were judged related to cemiplimab and for grade 3 AEs 26% were related, most common being infection (no G4 AEs were recorded). There were 2 grade 5 AEs, (cardiorespiratory event not related and toxic epidermal necrolysis related to treatment). 4 patients discontinued treatment due to toxicity, 2 related to cemiplimab (11%). Conclusions: Single agent cemiplimab as a first line treatment for la/mPC in the EPIC-B trial demonstrates efficacy with a generally manageable toxicity profile. This study adds to the evidence that single agent cemiplimab is a viable treatment for la/mPC patients for whom chemotherapy is not an option. Clinical trial information: 95561634.