A phase II trial of cemiplimab alone or in combination with standard of care chemotherapy in locally advanced or metastatic penile carcinoma (EPIC Trial)

TPS5094 Background: Penile cancer (PC) is rare but its incidence is increasing, with an increase of 21% over the last decade. The rarity of this cancer means a paucity of large prospective clinical trial data to guide the management of locally advanced/metastatic penile cancer (la/mPC). Cisplatin containing combination chemotherapy regimens are widely regarded as the standard of care (SOC) in this setting. However, with response rates of about 50% 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. Currently there are ongoing clinical trials exploring immunotherapy on penile carcinoma, however, none of these trials are looking at the combination of immunotherapy and chemotherapy. The novel immune checkpoint inhibitor cemiplimab has been approved for locally advanced and metastatic cutaneous squamous cell carcinoma (mcSCC). In view of this, we sought 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, open label, two arm phase II multi-centre trial of single agent cemiplimab versus cemiplimab + SOC chemotherapy in la/mPC, choice of arm decided by the investigator site based on chemotherapy eligibility. Eligibility includes patients with la/mPC who are candidates for immunotherapy +/- SOC chemotherapy (local UK centre choice of cisplatin/5FU or TPF or TIP regimes). 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, up to 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) post cycle 4 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). To date, 4 patients have been recruited from 2 centres with the aim to open all UK centres to recruitment by June 2022. The EPIC trial is NCRN badged. Clinical trial information: 95561634.