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

Plain English Summary

MRG003 Plus HX008 as First-Line Treatment for EGFR-Positive Locally Advanced or Metastatic Penile Squamous Cell Carcinoma is a Phase 1 clinical trial sponsored by Jiyan Liu studying Penile Cancer. This trial is testing a new combination of two drugs, MRG003 and HX008, as a first treatment for advanced penile cancer. It is for men with locally advanced or metastatic penile squamous cell carcinoma that has spread and expresses a specific protein called EGFR. Participants will receive the two study drugs intravenously every three weeks. The trial will monitor their response to treatment and any side effects. Currently, standard treatment for this condition involves chemotherapy, which has limited effectiveness and significant side effects. The trial aims to enroll 10 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Men aged 18 and older with confirmed penile squamous cell carcinoma that cannot be surgically removed or has spread to other parts of the body. Patients must have evidence of EGFR protein on their tumor cells and have not received prior treatment for advanced disease. Good general health is required, including adequate heart, blood, and organ function, and a performance status that allows for daily activities. Individuals with brain metastases (unless stable and treated), active infections, severe uncontrolled diseases, or certain autoimmune conditions may not be eligible. This trial is studying Penile Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see how many patients respond to the treatment by measuring the shrinkage of their tumors within 12 weeks, indicating the treatment's effectiveness. The specific primary outcome measures are: Objective response rate (ORR) (12 weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses the urgent need for more effective and less toxic treatments for advanced penile cancer, a rare disease with a poor prognosis and limited options after initial therapy. This research targets Penile Cancer, where improved treatment options are needed.

Investor Insight

This Phase 1 trial is an early step to evaluate a novel combination therapy for a rare cancer, potentially opening a new treatment avenue if successful, though approval probability is low at this earl Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific goals of this trial and how the study drugs work. Understand the potential benefits and risks, including common and serious side effects of MRG003 and HX008. Be prepared for regular clinic visits for drug infusions, blood tests, imaging scans, and to report any new symptoms or side effects. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 10 participants

Interventions

• DRUG: MRG003 — MRG003 (2.0 mg/kg, IV, Q3W). Treatment continues until disease progression, intolerable toxicity, withdrawal, death, or sponsor termination.
• DRUG: HX008 — HX008 (200 mg, IV, Q3W). Treatment continues until disease progression, intolerable toxicity, withdrawal, death, or sponsor termination.

Primary Outcomes

• Objective response rate (ORR) (12 weeks)

Secondary Outcomes

• Progression-free survival (PFS) (12 weeks)
• Disease control rate (DCR) (12 weeks)
• Duration of response (DoR) (12 weeks)
• Overall survival (OS) (12 weeks)

Full Eligibility Criteria

Inclusion Criteria:

1. Histologically and/or cytologically confirmed unresectable, locally advanced, or metastatic penile squamous cell carcinoma.
2. EGFR expression (defined as IHC 1+, 2+, or 3+) confirmed by the institutional pathology department using primary or metastatic tumor tissue samples.
3. No prior systemic therapy for advanced disease.
4. Male, aged ≥18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with a life expectancy ≥3 months.
6. At least one measurable lesion per RECIST 1.1 criteria.
7. 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.
8. Willing to provide written informed consent, with full understanding of the study requirements and commitment to comply with trial procedures and follow-up visits.

Exclusion Criteria:

1. Patients who have received prior systemic therapy before enrollment.
2. 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.
3. 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.
4. 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.
5. Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within the past 2 years. Replacement therapies (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) are permitted.
6. Positive serological virology test results, including HIV positivity, HBsAg positivity with detectable HBV DNA (≥2000 copies/mL), or HCV antibody positivity (eligible only if HCV RNA PCR-negative).
7. Major surgery within 4 weeks before enrollment, or prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
8. Administration of or plans to receive anti-cancer vaccines within 4 weeks before enrollment or during the study.
9. Clinically significant pleural effusion or ascites, as determined by the investigator to be unsuitable for enrollment.
10. Any other condition considered by the investigator to make the patient ineligible for the clinical study.

Trial Locations

• West China Hospital of Sichuan University, Chengdu, Sichuan, China

Frequently Asked Questions

Related Conditions

• Penile Cancer
• Squamous Cell Carcinoma
• EGFR-positive Cancers
• Metastatic Cancer
• Rare Cancers
• Oncology
• Targeted Therapy
• Immunotherapy
• Genitourinary Cancers
• Advanced Stage Cancer

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