MH-Penile-002: a phase II, prospective, single-arm trial of neoadjuvant anti-EGFR antibody-drug conjugate plus PD-1 inhibitor in penile cancer with challenging penile preservation or regional lymph node metastasis.

Emerging evidence suggests that combinations of antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) may be effective for advanced penile squamous cell carcinoma (PSCC). These findings support the translation of this strategy into the neoadjuvant setting, offering a novel approach for patients with locally advanced or regionally metastatic disease who have limited treatment options. This single-center, prospective, single-arm, phase II trial evaluates the efficacy and safety of neoadjuvant Becotatug Vedotin plus Pucotenlimab in EGFR-expressing PSCC patients with challenging penile preservation or regional lymph node metastasis. Utilizing a Simon's two-stage design, the primary endpoint is the investigator-assessed R0 resection rate. Secondary endpoints include the downstaging rate, objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, tumor regression grade (TRG), event-free survival (EFS), disease-free survival (DFS), and organ‑sparing rate. The study plans to enroll 60 patients with EGFR-expressing PSCC. Clinical trial registration: www.clinicaltrials.gov identifier is NCT07518979.