A multicenter phase II study of avelumab in patients with locally advanced or metastatic penile cancer (PC) who are unfit for, or have progressed on or after platinum-based chemotherapy: (ALPACA).

TPS7 Background: Squamous cell carcinoma of the penis is a rare and highly aggressive malignancy. Combination platinum-based chemotherapy is the standard of care in the metastatic setting. However, it is poorly tolerated and outcomes are dismal, underscoring an urgent unmet need for novel strategies. Since, penile cancers are often HPV-mediated and frequently overexpress PDL1, there is strong rationale to test the PDL1 inhibitor Avelumab, which is a well-tolerated drug in the setting of metastatic PC. Methods: This is a multicenter, single arm, phase 2 study of Avelumab (10mg/kg IV every 2 weeks) in patients with locally advanced or metastatic PC unfit for or progressed on platinum-based chemotherapy. A Simon’s two-stage design will be used where 9 patients will be enrolled in stage 1. If there is at least 1 response defined by iRECIST (complete response [iCR], partial response [iPR], or stable disease [iSD]) the study will proceed to stage 2, where an additional 15 patients will be enrolled. The primary objective is to demonstrate the anti-tumor activity of avelumab by objective response rate (ORR) according to (iRECIST). Secondary endpoints include: PFS, OS in patients determined to have PD-L1 positive tumors (including infiltrating immune cells) by the GMP verified Dako PD-L1 IHC 22C3 pharmDx test with thresholds of <1%, 1-49%, and ≥ 50% to define PD-L1 positivity, and in all enrolled patients. Secondary objectives also include assessing pathologic complete response rate (pCR) for patients undergoing surgery in the treatment time course, evaluation of safety and immunogenicity profile of Avelumab. The study is now open and actively accruing with further centres opening imminently. Funding Source: Pfizer. Clinical trial information: 03391479.