Becotatug vedotin plus sintilimab with chemoradiation for high-risk nasopharyngeal carcinoma

Becotatug Vedotin Combined With Sintilimab and Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma：A Multicenter, Randomized, Controlled, Phase 3 Trial

This trial tests whether adding becotatug vedotin before treatment and giving sintilimab with chemoradiation helps people with high‑risk locally advanced nasopharyngeal carcinoma live longer and avoid recurrence.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 266 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Guangxi Medical University (other)
• Drugs / interventions: sintilimab, chemotherapy, prednisone, radiation
• Locations: 1 site (Nanning, Guangxi)
• Trial ID: NCT07459296 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, open‑label phase III trial enrolling 266 patients with high‑risk locally advanced nasopharyngeal carcinoma (AJCC 9th edition: anyT N2-3M0 or T4N1M0). Participants are randomized 1:1 to an experimental arm receiving three cycles of neoadjuvant becotatug vedotin plus sintilimab followed by cisplatin‑based concurrent chemoradiotherapy (IMRT) with adjuvant sintilimab, or to a control arm receiving three cycles of gemcitabine plus cisplatin induction followed by the same chemoradiotherapy. The primary endpoint is 3‑year event‑free survival, with secondary endpoints including overall survival, locoregional failure‑free survival, distant metastasis‑free survival, objective response rate, adverse events, and quality of life. The trial also includes biomarker exploratory analyses (for example EGFR expression and PD‑L1 CPS) and predefined dose‑adjustment and toxicity management protocols.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18–70 with pathologically confirmed non‑keratinizing nasopharyngeal carcinoma staged anyT N2-3M0 or T4N1M0 (AJCC 9th), ECOG 0–1, and adequate blood, liver, and renal function.

Not a fit: Patients with distant metastasis, ECOG performance status >1, significant organ dysfunction, or non‑WHO type II/III histology are not eligible and are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could reduce recurrences and distant metastases and improve 3‑year event‑free and overall survival for patients with high‑risk locally advanced NPC.

How similar studies have performed: PD‑1 inhibitors plus chemotherapy have shown benefit in recurrent/metastatic NPC, but combining an antibody‑drug conjugate like becotatug vedotin with sintilimab in the curative, locally advanced setting is novel and not yet proven in phase III.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily participate in the study and sign the informed consent form in writing.
2. Aged 18-70 years, male or non-pregnant female.
3. Pathologically confirmed as nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated type, i.e., WHO type II or III).
4. Staged as anyT N2-3 or T4N1 (9th AJCC/UICC staging) without distant metastasis.
5. ECOG performance status score of 0-1.
6. Hemoglobin (HGB) ≥ 90 g/L, neutrophil count ≥ 1.5×10⁹/L, and platelet (PLT) count ≥ 100×10⁹/L.
7. Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN), and total bilirubin ≤ 1.5 times ULN.
8. Normal renal function: Creatinine clearance rate ≥ 60 ml/min (calculated using the Cockcroft-Gault formula).
9. Sexually active females of childbearing potential must agree to use effective contraceptive measures during treatment and for 1 year after the last administration of the study drug. Males who have sexual relations with females of childbearing potential must also agree to use effective contraceptive measures during treatment and for 1 year after the last administration of the study drug.

Exclusion Criteria:

1. Aged \> 70 years or \< 18 years.
2. Patients with recurrent or distant metastatic nasopharyngeal carcinoma.
3. Pathologically confirmed as keratinizing squamous cell carcinoma (WHO type I).
4. Patients who have previously received radiotherapy or systemic chemotherapy.
5. Positive for hepatitis B surface antigen (HBsAg) with hepatitis B virus DNA \> 1000 copies/mL or 200 IU/mL.
6. Positive for hepatitis C virus antibody (anti-HCV).
7. Patients with active autoimmune diseases, excluding type 1 diabetes mellitus, hypothyroidism controlled by replacement therapy, and skin diseases that do not require systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
8. Patients who received systemic glucocorticoids (equivalent to prednisone \> 10 mg/day) or other immunosuppressive therapy within 28 days prior to signing the informed consent form. Patients who received systemic glucocorticoids equivalent to prednisone ≤ 10 mg/day, inhaled or topical glucocorticoids are eligible for enrollment.
9. Patients with a history of active tuberculosis within the past year; patients with active tuberculosis that has been adequately treated for more than one year are eligible for enrollment. Patients with a history of other malignant tumors (except cured basal cell carcinoma or carcinoma in situ of the cervix).
10. Patients with a history of interstitial lung disease.
11. Patients who received live vaccines within 30 days prior to signing the informed consent form or plan to receive live vaccines in the near future.
12. Pregnant or lactating females.
13. Patients with a history of other malignant tumors within the past 5 years, except carcinoma in situ, adequately treated non-melanoma skin cancer, and papillary thyroid cancer.
14. Patients with known hypersensitivity to any component of gemcitabine, cisplatin, becotatug vedotin, or sintilimab.
15. Patients with known history of HIV infection.
16. Any other conditions deemed by the investigator to potentially affect the patient's ability to sign the informed consent form, cooperate with and participate in the study, or interfere with the interpretation of results, including symptomatic heart failure, unstable angina pectoris, myocardial infarction, active infections requiring systemic treatment, mental illnesses, or family/social factors.

Where this trial is running

Nanning, Guangxi

• The First Affiliated Hospital of Guangxi Medical University — Nanning, Guangxi, China (RECRUITING)

Study contacts

• Study coordinator: Min Kang, MD

Conditions: Nasopharyngeal Carcinoma, Becotatug Vedotin, Sintilimab, Concurrent Chemoradiotherapy