Adaptive immunotherapy for nasopharyngeal carcinoma

Adaptive Immunotherapy for Locoregional Nasopharyngeal Carcinoma: a Randomized, Controlled, Multicenter, Phase 3 Clinical Trial

This trial will test whether, after induction chemoimmunotherapy, low‑risk patients with undetectable EBV‑DNA can be safely treated with radiotherapy alone instead of concurrent chemoradiotherapy, and whether adding capecitabine to adjuvant immunotherapy improves outcomes for high‑risk patients with detectable EBV‑DNA or stable disease.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 802 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: toripalimab, chemotherapy, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07154069 on ClinicalTrials.gov

What this trial studies

This is a phase 3, single‑center randomized trial that adapts post‑induction treatment based on tumor response and circulating EBV‑DNA. All participants receive three cycles of GP induction chemotherapy combined with a PD‑1 inhibitor, then are stratified by post‑induction response and EBV‑DNA level. Low‑risk patients with complete or partial response and undetectable EBV‑DNA are randomized to radical radiotherapy alone versus concurrent chemoradiotherapy to compare event‑free survival and toxicity. High‑risk patients with stable disease or detectable EBV‑DNA are randomized to adjuvant capecitabine plus immunotherapy versus adjuvant immunotherapy to test for improved event‑free survival.

Who should consider this trial

Good fit: Ideal candidates are adults 18–65 with newly diagnosed non‑keratinizing stage II–III nasopharyngeal carcinoma, ECOG 0–1, adequate organ function, who completed three cycles of GP induction chemotherapy plus a PD‑1 inhibitor and have either CR/PR with undetectable post‑induction EBV‑DNA (low‑risk) or SD/detectable post‑induction EBV‑DNA (high‑risk).

Not a fit: Patients unlikely to benefit include those with keratinizing histology, stages outside II–III, poor performance status or organ dysfunction, or those who do not meet the required induction response or EBV‑DNA criteria.

Why it matters

Potential benefit: If successful, this approach could spare low‑risk patients the added toxicity of concurrent chemotherapy while maintaining event‑free survival and could improve event‑free survival for high‑risk patients by adding capecitabine to adjuvant immunotherapy.

How similar studies have performed: Prior phase 3 trials adding immunotherapy to induction chemotherapy have improved event‑free survival and prospective studies have shown that undetectable post‑induction EBV‑DNA identifies a low‑risk group, while de‑intensification trials have reduced toxicity in selected patients.

Eligibility criteria

Inclusion Criteria:

* 18-65 years;
* Newly diagnosed, pathologically confirmed non-keratinizing carcinoma (according to WHO criteria);
* Locoregionally advanced nasopharyngeal carcinoma (Stage II-III) as defined by the 9th edition of the American Joint Committee on Cancer (AJCC) staging system;
* ECOG performance status: 0-1;
* Adequate bone marrow function: white blood cell count \> 4 × 10⁹/L, hemoglobin \> 90 g/L, platelet count \> 100 × 10⁹/L;
* Normal renal and hepatic function: total bilirubin ≤ 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; creatinine clearance ≥ 60 mL/min;
* Normal thyroid function, amylase, lipase, pituitary function;
* Completion of 3 cycles of GP regimen induction chemotherapy combined with PD-1 inhibitor immunotherapy;
* Patients must provide signed informed consent and be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures;
* Female participants of childbearing potential must agree to use reliable contraceptive methods (e.g., condoms, regular use of oral contraceptives as prescribed) from screening until one year after treatment.

Exclusion Criteria:

* T3N0-1, according to the American Joint Committee on Cancer (AJCC) Staging System, 9th Edition;
* Disease progression after induction therapy;
* Hepatitis B surface antigen (HBsAg) positive with HBV DNA \>1×10³ copies/mL, or anti-hepatitis C virus (HCV) antibody positive;
* Anti-HIV antibody positive or diagnosed with acquired immunodeficiency syndrome (AIDS);
* Active tuberculosis;
* Active, known, or suspected autoimmune disease. Exceptions include type 1 diabetes, hypothyroidism requiring hormone replacement therapy, and skin disorders not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia);
* History of interstitial lung disease or pneumonia requiring oral or intravenous steroid treatment within the past year;
* Chronic systemic glucocorticoid therapy or any other form of immunosuppressive therapy. Subjects using inhaled or topical corticosteroids are eligible;
* Uncontrolled cardiac disease;
* Pregnant or lactating women;
* History or current diagnosis of another malignancy, except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or papillary thyroid carcinoma;
* Known allergy to macromolecular protein preparations or any component of toripalimab;
* Active infection requiring systemic treatment within one week prior to enrollment;
* Administration of a live vaccine within 30 days before the first dose of toripalimab;
* History of organ transplantation;
* Contraindications to MRI examination, which would prevent the completion of required imaging;
* Any other condition deemed by the investigators to potentially compromise patient safety or compliance.

Where this trial is running

Guangzhou, Guangdong

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

Study contacts

• Study coordinator: Ling-Long Tang

Conditions Nasopharyngeal Cancinoma