Neoadjuvant Pucotenlimab and Becotatug Vedotin for Locally Advanced Penile Cancer

Inclusion Criteria:

1. Aged 18-75 years, biologically male.
2. Histologically confirmed penile squamous cell carcinoma, stage T4 any N M0 or any T N2-N3 M0 without distant metastasis.
3. Treatment-naive; or relapsed patients with ≥12 months interval from last prior systemic therapy.
4. At least one measurable target lesion per RECIST 1.1.
5. ECOG performance status 0-2.
6. Adequate bone marrow, liver and renal function as predefined lab thresholds.
7. Expected survival ≥12 months.
8. No severe uncontrolled organ dysfunction.
9. Able to understand and voluntarily sign written informed consent.

Exclusion Criteria:

1. Pre-existing grade ≥2 peripheral neuropathy interfering daily activities.
2. Prior neoadjuvant therapy for penile cancer; previous use of PD-1/PD-L1 inhibitors or EGFR ADCs including becotatug vedotin.
3. Known hypersensitivity to pucotenlimab, becotatug vedotin or excipients.
4. Active malignancy within 5 years (excluding cured basal cell skin carcinoma and low-risk prostate cancer).
5. Uncontrolled severe cardiovascular disease, active hepatitis B/C, active infection requiring antibiotics within 2 weeks before enrollment.
6. Live vaccine administered within 30 days before first dosing.
7. HIV infection, autoimmune disease requiring systemic therapy within 2 years, long-term systemic immunosuppressants.
8. Other conditions judged by investigators to interfere with study treatment or assessment.