Phase I Study of Becotatug Vedotin for Safety and Efficacy in EGFR-Positive Pediatric Relapsed/Refractory or Metastatic Solid Tumors

NCT07584499 | Recruiting Phase 1

• 2 other identifiers: MRG003-pediatirc-001Sun Yat-sen University Cancer
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nasopharyngeal Carcinoma; Lymphoepithelial Carcinoma; Neuroblastoma; Medulloblastoma; Wilms Tumor; Atypical Teratoid/Rhabdoid Tumors; Head and Neck Squamous Cell Carcinoma (HNSCC) - Recurrent/Metastatic (R/M); Rhabdomyosarcoma; Diffuse Intrinsic Pontine Gliomas; Other EGFR-positive Pediatric Solid Tumors Deemed Eligible by the Investigator

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities

  DLTs are defined as treatment-related adverse events or laboratory abnormalities (excluding hypersensitivity reactions) that meet CTCAE v4.03 grade 3-4 criteria and occur during the first 21 days of treatment, including: * Grade 4 neutropenia lasting \>7 days * Grade 3 thrombocytopenia lasting \>7 days or any grade 4 thrombocytopenia * Grade 3 febrile neutropenia requiring antibiotic therapy * Grade 3-4 hepatic, renal, cardiovascular, ocular, or neurological toxicities * Uncontrolled grade 3-4 skin, gastrointestinal, or other systemic toxicities

  First 21-day treatment cycle (Cycle 1)

Study Arms (1)

Becotatug Vedotin (MRG003) Phase I Dose-Escalation & Expansion in EGFR-Positive Pediatric R/M Solid

EXPERIMENTAL

This is a single-arm, open-label study where all enrolled participants receive Becotatug Vedotin (MRG003), a novel EGFR-targeted antibody-drug conjugate (ADC), as monotherapy. Intervention Details Study Drug: Becotatug Vedotin (MRG003) for Injection Route of Administration: Intravenous (IV) infusion over 30 minutes to 3 hours Dosing Schedule: Every 3 weeks (Q3W) on Day 1 of each 21-day cycle Maximum Treatment Duration: Up to 8 cycles (24 weeks) Dose Levels: Ia Dose-Escalation Phase: 4 planned dose levels (1.0, 1.5, 2.0, 2.3 mg/kg) Starting dose: 1.0 mg/kg (modified accelerated titration design, 1 patient per cohort) Subsequent doses: Standard 3+3 design Ib Dose-Expansion Phase: All patients receive the determined Recommended Phase II Dose (RP2D)

Drug: Becotatug Vedotin

Interventions

Becotatug Vedotin DRUG

Study Drug: Becotatug Vedotin (MRG003) for Injection (lyophilized powder, 20 mg/vial) Route: Intravenous (IV) infusion over 30 minutes to 3 hours Schedule: Every 3 weeks (Q3W) on Day 1 of each 21-day cycle Maximum Treatment Duration: Up to 8 cycles (24 weeks); patients with confirmed clinical benefit (objective response or stable disease) may continue treatment beyond 8 cycles until disease progression, unacceptable toxicity, withdrawal of consent, or study termination

Becotatug Vedotin (MRG003) Phase I Dose-Escalation & Expansion in EGFR-Positive Pediatric R/M Solid

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Recurrence; Neoplasm Metastasis; Nasopharyngeal Carcinoma; Rhabdomyosarcoma; Neuroblastoma; Medulloblastoma; Wilms Tumor; Rhabdoid Tumor

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Yizhuo Zhang

CONTACT

020-87342460; zhangyzh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, director of department of pediatric oncology

Study Record Dates

• First Submitted: May 7, 2026
• First Posted: May 13, 2026
• Study Start: May 30, 2026
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2028
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)