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.
Patients who have received prior systemic therapy before enrollment.
History of other malignancies, except for cured carcinoma in situ of the cervix, basal cell carcinoma of the skin, or other malignancies that have been disease-free for at least 5 years.
Presence of central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may be eligible if they have been stable for at least 6 months, show no disease progression on imaging within 4 weeks before treatment, have no neurological symptoms, demonstrate no evidence of new or enlarging brain metastases, and have discontinued radiation, surgery, or steroid therapy for brain metastases at least 28 days prior to the first dose. Carcinomatous meningitis is excluded regardless of clinical stability.
Severe or uncontrolled concurrent diseases, including uncontrolled infections, active tuberculosis, uncontrolled diabetes, cardiovascular diseases (such as NYHA Class III or IV heart failure, second-degree or higher heart block, myocardial infarction within the past 12 months, unstable arrhythmia or angina, or cerebral infarction within the past 6 months), pulmonary diseases (such as interstitial lung disease, chronic obstructive pulmonary disease, or a history of symptomatic bronchospasm), deep vein thrombosis or pulmonary embolism within the past 12 months, or decompensated cirrhosis.
Single group
MRG003
DrugMRG003 (2.0 mg/kg, IV, Q3W). Treatment continues until disease progression, intolerable toxicity, withdrawal, death, or sponsor termination.
HX008
DrugHX008 (200 mg, IV, Q3W). Treatment continues until disease progression, intolerable toxicity, withdrawal, death, or sponsor termination.
Objective response rate (ORR)
CT scans
Progression-free survival (PFS)
CT scans and follow-up by phone
Disease control rate (DCR)
CT scans
Duration of response (DoR)
CT scans and follow-up by phone
Overall survival (OS)
Follow-up by phone
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Jiyan Liu
Lead sponsor
West China Hospital
Sponsor institution
West China Hospital
Collaborator
Lepu Medical Technology (Beijing) Co., Ltd.
Collaborator
