Becotatug Vedotin for EGFR-positive relapsed, refractory, or metastatic pediatric solid tumors

A Phase I Clinical Study to Explore the Safety and Efficacy of Becotatug Vedotin in Pediatric Patients With EGFR-Positive Relapsed/Refractory or Metastatic Solid Tumors

This trial will test Becotatug Vedotin, an EGFR-targeted antibody-drug conjugate, to see if it is safe and helps children aged 2–18 with EGFR-positive relapsed, refractory, or metastatic solid tumors.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 51 (estimated)
• Ages: 2 Years to 18 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07584499 on ClinicalTrials.gov

What this trial studies

This is a Phase I, multicenter, non-randomized, single-arm, open-label trial that gives pediatric patients with EGFR-positive relapsed/refractory or metastatic solid tumors Becotatug Vedotin and monitors safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity. The drug is an anti-EGFR antibody linked to the cytotoxin monomethyl auristatin E (MMAE) designed to deliver chemotherapy directly to EGFR-expressing cancer cells. Adult Phase I data showed a manageable safety profile and encouraging response rates in EGFR-positive head and neck and nasopharyngeal cancers, and this trial extends testing into children. Patients will undergo EGFR biomarker testing before enrollment and will be followed with clinical exams and imaging to document adverse events and tumor responses.

Who should consider this trial

Good fit: Ideal candidates are children aged 2–18 with pathologically confirmed EGFR-positive relapsed, refractory, or metastatic solid tumors (such as HNSCC, nasopharyngeal carcinoma, rhabdomyosarcoma, or neuroblastoma) who meet organ-function and life-expectancy requirements and agree to EGFR testing.

Not a fit: Patients without EGFR-positive tumors, those outside the 2–18 age range, or patients with rapidly declining performance status or uncontrolled medical conditions are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, Becotatug Vedotin could become a targeted treatment option that shrinks tumors while keeping side effects manageable for children with EGFR-positive relapsed or metastatic solid tumors.

How similar studies have performed: Adult Phase I trials of Becotatug Vedotin reported a manageable safety profile and objective response rates around 29–31% in nasopharyngeal and head and neck cancers, but pediatric data are limited.

Eligibility criteria

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.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Yizhuo Zhang

Conditions: Head and Neck Squamous Cell Carcinoma - Recurrent/Metastatic, Nasopharyngeal Carcinoma, Lymphoepithelial Carcinoma, Rhabdomyosarcoma, Neuroblastoma, Medulloblastoma, Wilms Tumor, Atypical Teratoid/Rhabdoid Tumors