Becotatug Vedotin (MRG003) With PD-1 Blockade and Chemoradiotherapy in High-Risk Locoregionally Advanced Nasopharyngeal Carcinoma

NCT07524413 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 2025-FXY-502-FLK
• Study Type: interventional
• Target: 514
• Locations: 0 countries
• Sites: N/A

Brief Summary

This randomized controlled trial aims to evaluate the efficacy and safety of Becotatug Vedotin (MRG003), an antibody-drug conjugate (ADC), combined with the PD-1 inhibitor Pucotenlimab as induction therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (NPC), compared to the standard gemcitabine and cisplatin (GP) regimen combined with Pucotenlimab, followed by concurrent chemoradiotherapy (CCRT) and adjuvant immunotherapy.

Conditions

Nasopharyngeal Cancinoma (NPC); Nasopharyngeal Cancer

Keywords

PD-1 antibody; Antibody-Drug Conjugate; MRG003; Becotatug Vedotin; Pucotenlimab

Outcome Measures

Primary Outcomes (2)

• Post-induction Therapy Complete Response Rate (post-IT CRR)

  The proportion of patients achieving complete response following induction therapy

  Within 9 to 21 days after the last dose of induction therapy

• Event-Free Survival (EFS)

  From date of randomization until the date of first documented locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.

  3 years & 5 years

Secondary Outcomes (8)

• Overall survival (OS)

  3 years & 5 years

• Distant Metastasis-Free Survival (DMFS)

  3 years & 5 years

• Locoregional Recurrence-Free Survival (LRRFS)

  3 years & 5 years

• Adverse Events (AEs)

  3 years & 5 years

• Patient-Reported Adverse Events (PRO-CTCAE)

  At the end of each treatment cycle (each cycle is 21 days), from Cycle 1 of induction therapy through Cycle 6 of adjuvant therapy

Other Outcomes (1)

• Correlation of Tumor, Peripheral Blood, and Fecal Biomarkers with Treatment Efficacy and Patient Prognosis

  3 years & 5 years

Study Arms (2)

ADC + PD-1Inhibitor Induction Therapy

EXPERIMENTAL

Induction Therapy (3 cycles, Q3W): Becotatug Vedotin (MRG003) 2.0 mg/kg, intravenous infusion, Day 1 + Pucotenlimab 200 mg, intravenous infusion, Day 1; Concurrent Chemoradiotherapy (CCRT): Intensity-modulated radiotherapy (IMRT): 70 Gy in 33 fractions, once daily, 5 days per week + Cisplatin 100 mg/m², intravenous infusion, Day 1 (2 cycles, Q3W); Adjuvant Immunotherapy (6 cycles, Q3W): Pucotenlimab 200 mg, intravenous infusion, Day 1

Drug: Becotatug Vedotin; Drug: Pucotenlimab; Radiation: intensity-modulated radiotherapy; Drug: Cisplatin

GP + PD-1 Inhibitor Induction Therapy

ACTIVE COMPARATOR

Induction Therapy (3 cycles, Q3W): Gemcitabine 1000 mg/m², intravenous infusion, Days 1 and 8 + Cisplatin 80 mg/m², intravenous infusion, Day 1 + Pucotenlimab 200 mg, intravenous infusion, Day 1; Concurrent Chemoradiotherapy (CCRT): Intensity-modulated radiotherapy (IMRT): 70 Gy in 33 fractions, once daily, 5 days per week + Cisplatin 100 mg/m², intravenous infusion, Day 1 (2 cycles, Q3W); Adjuvant Immunotherapy (6 cycles, Q3W): Pucotenlimab 200 mg, intravenous infusion, Day 1

Drug: Pucotenlimab; Drug: Gemcitabine + cisplatin (GP); Radiation: intensity-modulated radiotherapy; Drug: Cisplatin

Interventions

Becotatug Vedotin DRUG

Induction Therapy: Becotatug Vedotin (MRG003) 2.0 mg/kg, intravenous infusion, Day 1 (3 cycles, Q3W)

ADC + PD-1Inhibitor Induction Therapy

Pucotenlimab DRUG

Induction Therapy: Pucotenlimab 200 mg, intravenous infusion, Day 1 (3 cycles, Q3W); Adjuvant Therapy: Pucotenlimab 200 mg, intravenous infusion, Day 1 (6 cycles, Q3W)

ADC + PD-1Inhibitor Induction Therapy; GP + PD-1 Inhibitor Induction Therapy

Gemcitabine + cisplatin (GP) DRUG

Induction Therapy (3 cycles, Q3W): Gemcitabine 1000 mg/m², intravenous infusion, Days 1 and 8 Cisplatin 80 mg/m², intravenous infusion, Day 1

GP + PD-1 Inhibitor Induction Therapy

intensity-modulated radiotherapy RADIATION

70 Gy in 33 fractions, once daily, 5 days per week

ADC + PD-1Inhibitor Induction Therapy; GP + PD-1 Inhibitor Induction Therapy

Cisplatin DRUG

Concurrent Cisplatin: 100 mg/m², intravenous infusion, Day 1 (2 cycles, Q3W) during radiation

ADC + PD-1Inhibitor Induction Therapy; GP + PD-1 Inhibitor Induction Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥ 18 years at the time of diagnosis, regardless of sex
• \. Histologically confirmed newly diagnosed nasopharyngeal carcinoma (NPC) of non-keratinizing carcinoma histology (WHO classification)
• \. Locoregionally advanced NPC staged as T4N2 or T1-4N3 according to the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 9th edition staging system. All patients must undergo the following evaluations prior to initiation of any treatment to confirm clinical staging: complete medical history and physical examination, complete blood count (CBC) and biochemistry panel, plasma Epstein-Barr virus (EBV) DNA titer and serology, nasopharyngoscopy, magnetic resonance imaging (MRI) of the head and neck, chest X-ray or computed tomography (CT) of the chest, abdominal ultrasound, and bone scintigraphy. 18F-fluorodeoxyglucose positron emission tomography/CT (¹⁸F-FDG PET/CT) may be used as a substitute for the latter three imaging modalities.
• \. At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• \. Willing to provide archived tumor tissue (primary or metastatic lesion, obtained within 2 years prior to enrollment) or fresh biopsy specimen. Patients unable to provide tumor tissue may still be enrolled at the investigator's discretion, provided all other eligibility criteria are met.
• \. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to first dose
• \. Adequate organ function, as defined by the following laboratory parameters, obtained within 4 weeks prior to screening, with no blood transfusions, hematopoietic growth factors, or thrombopoietic agents administered during this period: a) Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; white blood cell count \> 4 × 10⁹/L; hemoglobin \> 90 g/L; platelet count \> 100 × 10⁹/L; b) Hepatic and renal function: Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 × ULN; alkaline phosphatase (ALP) ≤ 2.5 × ULN; creatinine clearance ≥ 60 mL/min; urinary protein ≤ 2+ or ≤ 1000 mg/24 hours; c) Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (patients receiving stable low-dose anticoagulation therapy, such as aspirin 100 mg/day, are permitted)

You may not qualify if:

• \. Willing and able to provide written informed consent and to comply with all protocol-specified requirements, including scheduled visits, treatment administration, laboratory assessments, and other study procedures
• \. Patients of reproductive potential must agree to use effective contraception from the time of informed consent through 6 months after the last dose of study treatment. Women of childbearing potential (WOCBP), defined as premenopausal women and women within 2 years of menopause, must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment.
• \. History of any other malignancy within the past 5 years, with the exception of curatively treated cervical carcinoma in situ, papillary thyroid carcinoma, or basal cell carcinoma of the skin
• \. Prior receipt of any anti-tumor therapy for nasopharyngeal carcinoma, or any of the following: a) Any ADC drug with a monomethyl auristatin E (MMAE) payload within 3 months prior to first dose; b) Any investigational drug from another clinical trial within 28 days prior to first dose; c) Major surgery within 28 days prior to first dose without full recovery, or planned major surgery within the first 12 weeks after initiation of study treatment
• \. Positive human immunodeficiency virus antibody (HIV-Ab); active tuberculosis; active hepatitis B virus infection (HBV-DNA \> 1 × 10³ copies/mL); or active hepatitis C virus infection (HCV antibody positive and HCV-RNA above the lower limit of detection)
• \. History of primary immunodeficiency, or active autoimmune disease requiring immunosuppressive therapy or systemic corticosteroids (≥ 10 mg/day prednisone or equivalent) within 2 weeks prior to enrollment. The following conditions are exempt: type 1 diabetes mellitus; hypothyroidism (including autoimmune thyroid disease) stable on hormone replacement therapy; psoriasis, vitiligo, or alopecia not requiring systemic treatment; and use of topical or inhaled corticosteroids, or short-term (≤ 7 days) systemic corticosteroids for prophylaxis or treatment of non-autoimmune, non-recurrent allergic conditions
• \. Uncontrolled cardiac disease, including any of the following: (1) heart failure of New York Heart Association (NYHA) Class ≥ 2; (2) unstable angina; (3) myocardial infarction within the past 1 year; (4) prolonged QT interval (QTc \> 450 ms in males or QTc \> 470 ms in females), complete left bundle branch block, third-degree atrioventricular block, or supraventricular or ventricular arrhythmia requiring treatment or intervention
• \. Hypertension inadequately controlled with two antihypertensive agents (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg)
• \. Poorly controlled blood glucose, defined as: (a) fasting blood glucose \> 10 mmol/L on two occasions, or (b) glycated hemoglobin (HbA1c) \> 8%; or concurrent diabetic gangrene
• \. History of interstitial lung disease (ILD) or pulmonary inflammation requiring steroid treatment (including pulmonary fibrosis and radiation pneumonitis), current ILD or pulmonary inflammation, or imaging findings at screening that cannot exclude suspected ILD or pulmonary inflammation
• \. Concurrent pulmonary disease causing clinically severe respiratory impairment, including but not limited to: (a) any underlying pulmonary condition (e.g., pulmonary embolism, severe asthma, or severe chronic obstructive pulmonary disease \[COPD\] within 3 months prior to screening); (b) restrictive lung disease; (c) history of or concurrent interstitial pneumonitis, radiation pneumonitis, severe COPD, severe pulmonary insufficiency, or symptomatic bronchospasm
• \. Unstable thromboembolic events requiring therapeutic intervention within 6 months prior to screening, including deep vein thrombosis, arterial thrombosis, or pulmonary embolism; catheter-related thrombosis is exempt
• \. Pregnant or breastfeeding women (pregnancy testing should be considered for sexually active women of childbearing potential)
• \. Known hypersensitivity to any component of Pucotenlimab or Becotatug Vedotin (MRG003) (including histidine, histidine hydrochloride, sucrose, mannitol, and polysorbate 80), or a history of Grade ≥ 3 hypersensitivity reaction to any macromolecular protein preparation or monoclonal antibody
• \. Serious infection (CTCAE Grade \> 2) within 4 weeks prior to first dose, including but not limited to severe pneumonia, bacteremia, sepsis, or active tuberculosis

Sponsors & Collaborators

• Sun Yat-sen University: lead

MeSH Terms

Conditions

Nasopharyngeal Neoplasms

Interventions

Gemcitabine; Cisplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Central Study Contacts

Jun Ma

CONTACT

+862087343469; majun2@mail.sysu.edu.cn

Wei Jiang

CONTACT

+862087342370; jiangwei@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 30, 2026
• First Posted: April 13, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2032
• Last Updated: April 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share