Overview

There is a significant unmet medical need for effective therapies for pediatric relapsed/refractory solid tumors. EGFR is highly and stably expressed in multiple pediatric solid tumor subtypes, and adult Phase I data of Becotatug Vedotin demonstrated a manageable safety profile and promising antitumor activity in EGFR-positive advanced solid tumors.This is a multicenter, non-randomized, single-arm, open-label Phase I clinical trial sponsored by Sun Yat-sen University Cancer Center (SYSUCC). The trial evaluates the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary efficacy of Becotatug Vedotin-an EGFR-targeted antibody-drug conjugate (ADC)-in pediatric patients with EGFR-positive relapsed/refractory or metastatic solid tumors.

Eligibility

Inclusion Criteria:

• All participants must meet all of the following criteria to be eligible for enrollment:

Informed Consent: The patient (and/or legal guardian, as age-appropriate) fully understands the study, voluntarily agrees to participate, and signs a written informed consent form (ICF). A separate biomarker consent form is required for EGFR testing prior to screening.

Age: 2 to 18 years old at the time of consent. Life Expectancy: Estimated overall survival of at least 3 months.

Histologically Confirmed Disease: Pathologically confirmed relapsed/refractory or metastatic EGFR-positive solid tumor, belonging to one of the following subtypes:

Head and neck squamous cell carcinoma, nasopharyngeal carcinoma, or lymphoepithelial carcinoma that progressed during or after at least one line of platinum-based chemotherapy and PD-1/PD-L1 inhibitor therapy Rhabdomyosarcoma Neuroblastoma Medulloblastoma Wilms tumor Atypical teratoid/rhabdoid tumors (AT/RTs) Diffuse intrinsic pontine gliomas (DIPGs) Other EGFR-positive solid tumor subtypes deemed eligible by the investigator Measurable Disease: At least one measurable tumor lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria (longest diameter ≥10 mm; pathological lymph node short axis ≥15 mm).

Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

Adequate Bone Marrow Function:

Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L Platelet count ≥75 × 10⁹/L Hemoglobin ≥80 g/L Exception for patients with bone marrow involvement: ANC ≥1.0 × 10⁹/L, platelets ≥50 × 10⁹/L, hemoglobin ≥75 g/L

Adequate Hepatic and Renal Function:

Serum creatinine ≤1.5 × upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN Total bilirubin ≤1.5 × ULN Exception for patients with liver involvement: AST/ALT ≤5 × ULN, total bilirubin ≤3 × ULN

Exclusion Criteria:

• Participants will be excluded from the study if they meet any of the following criteria:

Hypersensitivity: Known hypersensitivity to any component of Becotatug Vedotin (MRG003) or its excipients.

Symptomatic CNS Metastases: Presence of symptomatic central nervous system (CNS) metastases.

Prior Malignancies: History of other primary malignant tumors, except for:

Locally excised basal cell or squamous cell carcinoma of the skin Cervical carcinoma in situ Any prior malignancy that has been in complete remission for ≥3 years without treatment Note: Melanoma (any stage) is explicitly excluded

Significant Liver Disease: Clinically significant liver disease, including:

Positive hepatitis C virus (HCV) antibody Chronic active hepatitis B (HBV DNA \>20,000 IU/mL) HIV Infection: Known human immunodeficiency virus (HIV) infection. Severe Ocular Abnormalities: History of severe ophthalmologic conditions, such as severe dry eye syndrome or exposure keratitis.

Uncontrolled Systemic Diseases: Severe or uncontrolled medical conditions, including:

Interstitial lung disease or pneumonitis Active autoimmune diseases requiring systemic immunosuppressive therapy

Cardiac Disease: Clinically significant cardiac dysfunction or cardiac disease, including:

Congestive heart failure (New York Heart Association Class ≥II) Uncontrolled arrhythmias QTc interval prolongation \>450 ms (males) or \>470 ms (females) Recent Antitumor Therapy: Received any systemic antitumor therapy (chemotherapy, biological therapy, immunotherapy, targeted therapy) within 3 weeks prior to the first dose of study drug, and have not recovered to CTCAE v4.03 Grade ≤1 (except alopecia).

Recent Major Surgery: Underwent major surgical procedure within 3 weeks prior to the first dose of study drug.

Planned Surgery: Planned surgical procedure during the study period, or any surgery deemed necessary by the investigator.

Prior EGFR Therapy Toxicity: History of severe skin toxicity caused by prior EGFR-targeted therapy, or chronic skin disease requiring ongoing oral or intravenous treatment.

Other Significant Risks: Any other concurrent medical condition that, in the investigator's judgment, would increase the risk of toxicity or compromise the patient's ability to complete the study.