A phase II trial of cemiplimab alone or in combination with standard of care chemotherapy in locally advanced or metastatic penile carcinoma (EPIC trial).
Authors: Bahl Amit , Foulstone Emily , Ashurst Lauren , Renninson Emily , White Paul , Bravo Alicia , Afshar Mehran , Alifrangis Constantine , Venugopal Balaji , Thomson Alastair , Tran Anna , Barber Jim , Dearden Helen Clare , Kent Christopher , Kumar Vivekanandan , Callaway Mark , Challapalli Amarnath 
Published: January 2024

TPS14 Background: Penile cancer is rare, <1% of male malignancies diagnosed each year, but its incidence is increasing with an 18% increase over the last decade projected to rise a further 9% in the next 10 years. Patients with locally advanced/metastatic penile cancer (la/mPC) have very few treatment options and there is a lack of clinical trial data to guide management. Cisplatin containing combination chemotherapy regimens are regarded as the standard of care (SOC) in this setting. However, with response rates of 50% or less there is a need to further improve treatment outcomes. PDL1 is upregulated in 40–60% of PC cases and is correlated with poor prognosis making a case for immunotherapy as a treatment for la/mPC. The PD-1 inhibitor cemiplimab is approved for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (SCC) suggesting efficacy against penile SCC. The EPIC trial was set up to evaluate the benefit and safety of cemiplimab alone, or, in combination with SOC chemotherapy in patients with la/mPC. Methods: This is a non-randomised, 2 arm, phase II multi-centre trial. Arm 1 cemiplimab + SOC chemotherapy (local site choice of cisplatin/5FU, TPF or TIP regimes); Arm 2 single agent cemiplimab. The choice of arm decided by the investigator site based on chemotherapy eligibility. 47 patients will be recruited from 10 UK centres: 29 patients into ARM 1 who will receive 4 cycles of cemiplimab 350mg IV q3 weekly + SOC chemotherapy, followed by single agent cemiplimab x 30 cycles (24 months total). 18 patients into ARM 2 who will receive single agent cemiplimab 350mg IV q3 weekly x 34 cycles (24 months total). The primary endpoint is clinical benefit rate (CBR) of cemiplimab: objective response rate (ORR) plus stable disease as assessed radiologically (RECIST 1.1) at 12 weeks from first dose in patients with la/mPC. Secondary end-points include safety, tolerability, CBR at 1, 2 and 3 years, ORR, progression-free survival, overall survival and assessment of patient health status and quality of life using the patient reported outcome measures EQ-5D-5L and EORTC QLQ-C30. Each arm will be analysed separately as a Fleming A’Hern study α=0.05 + power (1-β)=0.8. Arm 1 assumes 25% meeting the clinical end point is a poor treatment (p0=0.25) and 50% is a good treatment (p1=0.5). Arm 2 assumes 5% meeting the clinical end point is a poor treatment (p0=0.05) and 25% is a good treatment (p1=0.25). Progress: By February 2023 10 UK sites had been opened to recruitment. The first patient entered the trial in November 2021 and to date 25 patients have been recruited into Arm 1 and 10 into Arm 2. Opening sites was slower than anticipated following emergence from the COVID pandemic. However, a recruitment rate of 1-2 patients per month has shown the feasibility of running a trial for this rare patient population. Clinical trial information: ISRCTN95561634 .