MRG003 Plus HX008 as First-Line Treatment for EGFR-Positive Locally Advanced or Metastatic Penile Squamous Cell Carcinoma: A Prospective, Single-Arm, Phase I Clinical Trial
Penile squamous cell carcinoma (PSCC) is a rare malignancy, with stage IV patients exhibiting a 2-year overall survival (OS) rate of 21% and a 5-year survival rate of 0%. Both the National Comprehensive Cancer Network (NCCN) and European Association of Urology (EAU) guidelines recommend chemotherapy as the first-line treatment. However, the efficacy of chemotherapeutic agents in PSCC remains suboptimal, and options after chemotherapy failure are extremely limited. In recent years, targeted therapy and immunotherapy have demonstrated potential in treating this disease. Combination therapies based on chemotherapy, particularly chemoimmunotherapy combined with targeted therapy, have shown promising antitumor effects. Nevertheless, these regimens are associated with significant adverse effects and impose high physical demands on patients. Therefore, this study aims to explore a highly effective and low-toxicity first-line treatment regimen for advanced PSCC patients. The objective is to evaluate the combined therapeutic efficacy of an epidermal growth factor receptor (EGFR)-targeted antibody-drug conjugate (MRG003) and an immune checkpoint inhibitor (HX008) through a single-arm, phase I, prospective clinical trial.
• Histologically and/or cytologically confirmed unresectable, locally advanced, or metastatic penile squamous cell carcinoma.
• EGFR expression (defined as IHC 1+, 2+, or 3+) confirmed by the institutional pathology department using primary or metastatic tumor tissue samples.
• No prior systemic therapy for advanced disease.
• Male, aged ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with a life expectancy ≥3 months.
• At least one measurable lesion per RECIST 1.1 criteria.
• Adequate organ function (based on institutional laboratory reference ranges):
• Left ventricular ejection fraction (LVEF) ≥50%.
• Hematology:
• Hemoglobin (HGB) ≥90 g/L, White blood cell count (WBC) ≥3.0×10⁹/L, Absolute neutrophil count (ANC) ≥1.5×10⁹/L, Platelet count (PLT) ≥80×10⁹/L.
• Biochemistry:
• Total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN), AST/ALT ≤2.5×ULN (≤5×ULN if liver metastases present), Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (CrCl) ≥50 mL/min.
• Willing to provide written informed consent, with full understanding of the study requirements and commitment to comply with trial procedures and follow-up visits.