Adaptive Immunotherapy for Nasopharyngeal Carcinoma

NCT ID: NCT07154069

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 802 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-13
• Study Completion Date: 2033-09-30

Brief Summary

1. To assess whether radiotherapy alone is non-inferior to concurrent chemoradiotherapy with respect to event-free survival and superior in reducing treatment-related nausea in low-risk locoregionally advanced nasopharyngeal carcinoma patients who achieve complete or partial response and undetectable serum EBV-DNA following induction chemoimmunotherapy.

2. To evaluate whether adjuvant capecitabine and immunotherapy after concurrent chemoradiotherapy improves event-free survival compared to adjuvant immunotherapy in high-risk locoregionally advanced nasopharyngeal carcinoma patients with stable disease or detectable serum EBV-DNA after induction chemoimmunotherapy.

Detailed Description

Recent trials have demonstrated that for patients with locoregionally advanced nasopharyngeal carcinoma (NPC), the addition of immnotherapy to standard induction chemotherapy followed by concurrent chemoradiotherapy significantly improves event-free survival (EFS) (NCT03700476 and NCT03427827). However, current trials on immnotherapies lack specific biomarkers for risk stratification and adaptive treatment strategies.

Epstein-Barr virus (EBV) is closely associated with the development of NPC. Cell-free EBV-DNA released by NPC cells can be detected in peripheral blood and has been strongly correlated with patient prognosis. Prospective clinical trials (NCT03855020 and NCT04907370) have confirmed that patients with undetectable EBV-DNA after induction therapy exhibit significantly better EFS compared to those with detectable post-induction EBV-DNA.

Among low-risk patients with undetectable EBV-DNA after induction therapy, the 3-year EFS rate exceeds 90%. However, the combination of immunotherapy with concurrent cisplatin-based chemoradiotherapy also leads to significant treatment-related toxicities, with 74% of patients experiencing grade 3 or higher adverse events. Therefore, there is an urgent need to explore novel treatment strategies aimed at reducing toxicity in this patient population. Recent phase 3 multicenter randomized trials have demonstrated that de-intensification strategies omitting concurrent cisplatin chemotherapy significantly reduce treatment-related toxicities in both early-stage (NCT02633202) and locoregionally advanced NPC (NCT04907370), with reductions in grade 3 or higher adverse events by 29% and 11%, respectively.

Among high-risk patients with positive EBV-DNA after induction therapy, even with the combination of immuotherapy, the 3-year EFS remains suboptimal, ranging from 65% to 80%. There is a critical need for treatment intensification strategies to improve outcomes in this group. A recently completed multicenter, randomized, phase 3 trial (NCT02958111) demonstrated that adjuvant metronomic capecitabine (650 mg/m² twice daily) for one year following standard induction chemotherapy and concurrent chemoradiotherapy significantly improved 3-year EFS from 75.7% to 85.3% in high-risk locoregionally advanced NPC patients, with a manageable toxicity profile.

Therefore, the investigators propose the following scientific hypothesis: in low-risk patients who achieve complete or partial response and undetectable serum EBV-DNA following induction chemoimmunotherapy, radiotherapy alone can reduce the incidence of treatment-related adverse effects, without reducing survival; in high-risk patients with stable disease or detectable serum EBV-DNA, adjuvant capecitabine and immunotherapy can improve survival.

Conditions

Nasopharyngeal Cancinoma (NPC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low risk arm 1

Radiotherapy alone

Group Type: EXPERIMENTAL

Radical radiotherapy of nasopharynx and neck

Intervention Type: RADIATION

Radical radiotherapy of nasopharynx and neck

Toripalimab

Intervention Type: DRUG

Adjuvant Toripalimab (240mg day1, Q3W )

Low risk arm 2

Concurrent chemoradiotherapy

Group Type: ACTIVE_COMPARATOR

Radical radiotherapy of nasopharynx and neck

Intervention Type: RADIATION

Radical radiotherapy of nasopharynx and neck

Concurrent chemoradiotherapy (cCRT)

Intervention Type: DRUG

Concurrent chemoradiotherapy

Toripalimab

Intervention Type: DRUG

Adjuvant Toripalimab (240mg day1, Q3W )

High risk arm 1

Adjuvant capecitabine and immunotherapy after concurrent chemoradiotherapy

Group Type: EXPERIMENTAL

Radical radiotherapy of nasopharynx and neck

Intervention Type: RADIATION

Radical radiotherapy of nasopharynx and neck

Capecitabine

Intervention Type: DRUG

Adjuvant metronomic capecitabine (650 mg/m² twice daily) for one year

Concurrent chemoradiotherapy (cCRT)

Intervention Type: DRUG

Concurrent chemoradiotherapy

Toripalimab

Intervention Type: DRUG

Adjuvant Toripalimab (240mg day1, Q3W )

High risk arm 2

Adjuvant immunotherapy after concurrent chemoradiotherapy

Group Type: ACTIVE_COMPARATOR

Radical radiotherapy of nasopharynx and neck

Intervention Type: RADIATION

Radical radiotherapy of nasopharynx and neck

Concurrent chemoradiotherapy (cCRT)

Intervention Type: DRUG

Concurrent chemoradiotherapy

Toripalimab

Intervention Type: DRUG

Adjuvant Toripalimab (240mg day1, Q3W )

Interventions

Radical radiotherapy of nasopharynx and neck

Radical radiotherapy of nasopharynx and neck

Intervention Type: RADIATION

Capecitabine

Adjuvant metronomic capecitabine (650 mg/m² twice daily) for one year

Intervention Type: DRUG

Concurrent chemoradiotherapy (cCRT)

Concurrent chemoradiotherapy

Intervention Type: DRUG

Toripalimab

Adjuvant Toripalimab (240mg day1, Q3W )

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Ling-Long Tang

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ling-Long Tang

Role: CONTACT

tangll@sysucc.org.cn

02087343840

Facility Contacts

Ling-Long Tang

Role: primary

tangll@sysucc.org.cn

02087343840

Other Identifiers

B2025-489-01

Identifier Type: -

Identifier Source: org_study_id