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.
Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1.
Histologically confirmed penile squamous cell carcinoma with evidence of metastasis, and EGFR expression confirmed positive by immunohistochemistry (IHC).
At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST): non-lymph node lesions with a longest diameter ≥ 10 mm on computed tomography (CT) scan, or lymph node lesions with a short axis diameter ≥ 15 mm on CT scan; or evaluable cutaneous lesions per World Health Organization (WHO) criteria.
Diagnosis of another malignancy within 5 years prior to the first dose (excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radically resected carcinoma in situ).
Prior treatment with an ADC drug containing monomethyl auristatin E (MMAE) as the cytotoxic moiety, or prior treatment with a PD-(L)1 inhibitor.
Currently participating in an interventional clinical study, or having received other investigational agents or investigational device therapy within 4 weeks prior to the first dose.
History of active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapies (e.g., thyroid hormone, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic therapy.
Fudan University
Lead sponsor
Fujian Province Tumor Hospital
Collaborator
Shanghai GoBroad Cancer Hospital
Collaborator
Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
Collaborator