A Multicenter, Single-Arm, Exploratory Study of Becotatug Vedotin Combined With Pucotenlimab in the Treatment of EGFR-Positive Advanced Penile Cancer in Patients Who Are Intolerant to Chemotherapy or Have Failed Chemotherapy

Detailed Summary

Penile cancer is a rare malignant tumor of the male genitourinary system, with 95% being squamous cell carcinoma. Due to social factors, delayed diagnosis is common, leading to a high rate of lymph node metastasis (17%-45% at diagnosis), which significantly impairs quality of life and prognosis. The 5-year survival rate is 27% for patients with lymph node metastasis and 0%-17% for those with pelvic lymph node metastasis (N3). Current standard treatments recommended by guidelines include surgery and chemotherapy. However, the neoadjuvant TIP regimen (paclitaxel + ifosfamide + cisplatin) in locally advanced disease yields an objective response rate (ORR) of 50%, pathological complete response (pCR) rate of 10%, median progression-free survival (PFS) of 8.1 months, and median overall survival (OS) of 17.1 months. For advanced patients, no standard effective treatments exist after platinum-based chemotherapy resistance, highlighting an urgent need for more effective combination therapies. High expression of PD-L1 (30%-70%) and EGFR (40%-80%) is common in penile squamous cell carcinoma, especially in poorly differentiated, late-stage disease with lymph node metastasis. A prospective phase II study showed that toripalimab (immunotherapy) combined with nimotuzumab (anti-EGFR antibody) and paclitaxel-based chemotherapy, followed by consolidation surgery, achieved an ORR of 82.8%, pCR rate of 48.3%, 2-year OS rate of 72.4%, and 2-year PFS rate of 65.5%; 41.4% of patients had grade 3-4 treatment-related adverse events, with no treatment-related deaths. Although immune checkpoint inhibitors and anti-EGFR targeted therapy demonstrate preliminary antitumor activity in advanced penile cancer, their clinical efficacy remains suboptimal with substantial toxicities, thus warranting the development of more effective combinatorial therapeutic strategies.

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