Background: At present, penile cancer patients receiving chemotherapy with paclitaxel, ifosfamide and cisplatin or docetaxel, cisplatin and 5-fluorouracil have a lack of post-progression treatment, and some patients lose the opportunity for effective treatment due to inability to tolerate chemotherapy. Even though the epidermal growth factor receptor (EGFR) is ubiquitously expressed in penile squamous cell carcinoma, anti-EGFR-targeted drugs have not achieved significant survival benefit. Immune checkpoint inhibitors (ICIs) have achieved "de-tumor immune escape", and a small number of penile cancer cases have shown reactivity. However, only patients with high TMB, high PD-L1 expression, or MSI-H have benefited from ICIs. Antibody-drug conjugates (ADCs) have advanced rapidly in recent years, and HER2-targeted ADCs have shown significant efficacy in HER2-overexpressing urothelial carcinoma. HER2 ADC and ICI can simultaneously block HER2 and PD-1/PD-L1 signaling pathways, bridge PD-1-expressing T lymphocytes and HER2-expressing tumor cells, assist T cells to recognize and kill tumor cells, improve immunosuppression in the tumor microenvironment, and enhance the infiltration of immune cells into tumors. Recent cytology and animal studies have also shown that HER2-targeted ADCs exhibit significant anti-tumor activity in both HER2-positive and cisplatin-resistant penile cancers. Therefore, in order to explore the feasible and effective options for patients with advanced penile cancer who have progressed or are intolerant to cisplatin-based chemotherapy, a single-arm, single-center clinical study using Disitamab Vedotin combined with Toripalimab is proposed. Methods: About 20 patients with advanced penile cancer who have progressed or are intolerant to chemotherapy are planned to be enrolled with antibody-drug conjugates (Disitamab Vedotin for injection, 1 time/2 weeks, 2.0 mg/kg) and PD-1 (Toripalimab, 1 time/2 weeks, 3.0 mg/kg; or1 time/3 weeks, 240 mg/kg), regimen until the disease progresses or is intolerant. This study is expected to provide a basis for the treatment of advanced penile cancer using this regimen.