Serplulimab Combined With Induction Chemotherapy and Radiotherapy in Nasopharyngeal Carcinoma

NCT ID: NCT07177443

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 456 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-25
• Study Completion Date: 2031-12-31

Brief Summary

This phase III trial aims to evaluate the efficacy and safety of induction chemotherapy combined with serplulimab (induction/maintenance therapy) with omission of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).

Detailed Description

This multicenter phase III trial enrolls high-risk locally advanced nasopharyngeal carcinoma patients (AJCC 9th edition, Stage T1-3N2 [II] or T1-4N3/T4N1-2 [III]) who achieves ≥50% tumor regression (RECIST v1.1) and undetectable plasma EBV DNA after three cycles of GP induction chemotherapy (gemcitabine + cisplatin) combined with serplulimab. Eligible patients will be randomized to either:

Experimental arm: Radiotherapy alone followed by serplulimab maintenance, or Control arm: Cisplatin-based concurrent chemoradiotherapy (CCRT) followed by serplulimab maintenance.

Primary study endpoint

• 3-year event-free survival (EFS)

• 5-year overall survival (OS)

• incidence of treatment-induced vomiting Secondary study endpoints
• 3-year distant metastasis-free survival (DMFS)

• 3-year locoregional recurrence-free survival (LRFS)

• Quality of life (QoL) assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30 v3.0) and its head-and-neck cancer module (EORTC QLQ-H&N35 v1.0), both validated Chinese versions.

• Incidence rate of investigator-reported adverse events (AEs) ⑤ Incidence rate of patient-reported AEs

Conditions

Locally Advanced Nasopharyngeal Carcinoma

Study Design

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

Study Groups

Experimental arm

Radiotherapy

Group Type: EXPERIMENTAL

Radiotherapy

Intervention Type: RADIATION

Following induction therapy, eligible patients will receive radiotherapy alone or concurrent chemoradiotherapy per protocol. Photon or proton radiotherapy techniques were permitted. Prescribed doses were:

Primary tumor and metastatic lymph nodes: 70 Gy/33 fractions High-risk lymphatic drainage areas: 60 Gy/33 fractions Low-risk regions: 54 Gy/33 fractions

PTV dose specifications:

GTVnx: 70 Gy GTVnd: 66-70 Gy (reducible to 63 Gy for suspicious small nodes) CTV1: 60-62 Gy CTV2: 54-56 Gy All treatments will employ simultaneous integrated boost (SIB) intensity-modulated radiotherapy delivered once daily, 5 fractions per week.

Serplulimab

Intervention Type: DRUG

Serplulimab will be used in the induction phase for 3 cycles and the maintenance phase for 14 cycles.

Control arm

Cisplatin-based concurrent chemoradiotherapy (CCRT)

Group Type: ACTIVE_COMPARATOR

Radiotherapy

Intervention Type: RADIATION

Following induction therapy, eligible patients will receive radiotherapy alone or concurrent chemoradiotherapy per protocol. Photon or proton radiotherapy techniques were permitted. Prescribed doses were:

Primary tumor and metastatic lymph nodes: 70 Gy/33 fractions High-risk lymphatic drainage areas: 60 Gy/33 fractions Low-risk regions: 54 Gy/33 fractions

PTV dose specifications:

GTVnx: 70 Gy GTVnd: 66-70 Gy (reducible to 63 Gy for suspicious small nodes) CTV1: 60-62 Gy CTV2: 54-56 Gy All treatments will employ simultaneous integrated boost (SIB) intensity-modulated radiotherapy delivered once daily, 5 fractions per week.

Serplulimab

Intervention Type: DRUG

Serplulimab will be used in the induction phase for 3 cycles and the maintenance phase for 14 cycles.

Cisplatin

Intervention Type: DRUG

On days 64 and 85, patients will receive cisplatin chemotherapy at a dose of 100 mg/m² via intravenous infusion.

Interventions

Radiotherapy

Following induction therapy, eligible patients will receive radiotherapy alone or concurrent chemoradiotherapy per protocol. Photon or proton radiotherapy techniques were permitted. Prescribed doses were:

Primary tumor and metastatic lymph nodes: 70 Gy/33 fractions High-risk lymphatic drainage areas: 60 Gy/33 fractions Low-risk regions: 54 Gy/33 fractions

PTV dose specifications:

GTVnx: 70 Gy GTVnd: 66-70 Gy (reducible to 63 Gy for suspicious small nodes) CTV1: 60-62 Gy CTV2: 54-56 Gy All treatments will employ simultaneous integrated boost (SIB) intensity-modulated radiotherapy delivered once daily, 5 fractions per week.

Intervention Type: RADIATION

Serplulimab

Serplulimab will be used in the induction phase for 3 cycles and the maintenance phase for 14 cycles.

Intervention Type: DRUG

Cisplatin

On days 64 and 85, patients will receive cisplatin chemotherapy at a dose of 100 mg/m² via intravenous infusion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age at diagnosis: 18-65 years;

2. Pathologically confirmed treatment-naïve nasopharyngeal carcinoma of "non-keratinizing type (WHO classification)";

3. Locoregionally advanced nasopharyngeal carcinoma staged per the 9th edition of the American Joint Committee on Cancer (AJCC) staging system: Stage II (T1-3N2), Stage III(T1-4N3 or T4N1-2);

4. ECOG performance status: 0-1;

5. Post-induction therapy requirements:

Radiological assessment showing ≥50% tumor regression (RECIST 1.1) Undetectable plasma EBV DNA levels;

6. Adequate bone marrow function:

White blood cell count >4×10⁹/L Hemoglobin >90 g/L Platelet count >100×10⁹/L;

7. Normal hepatic/renal function:

Total bilirubin ≤1.5×upper limit of normal (ULN) AST/ALT ≤2.5×ULN Alkaline phosphatase ≤2.5×ULN Creatinine clearance ≥60 mL/min;

8. Normal results for:

Thyroid function tests Amylase and lipase Pituitary function Inflammatory/infection markers Cardiac enzymes Electrocardiogram

Additional requirements:

Pulmonary function tests for smokers >50 years Cardiac ultrasound + myocardial function tests for patients with ECG abnormalities or cardiovascular history (unless meeting exclusion criterion (8));

9. Signed informed consent with willingness/compliance to follow study schedules for treatment, follow-up, and laboratory tests;

10. For women of childbearing potential: Agreement to use reliable contraception (e.g., condoms, prescribed oral contraceptives) from screening until 1 year post-treatment.

Exclusion Criteria

1. Hepatitis B Virus (HBV) Infection:

HBsAg-positive with HBV DNA >1×10³ copies/mL (patients with controlled viremia [<1×10³ copies/mL] after antiviral therapy are eligible).

2. Hepatitis C Virus (HCV) Infection: Anti-HCV antibody-positive.

3. HIV/AIDS: Anti-HIV antibody-positive or diagnosed with acquired immunodeficiency syndrome (AIDS).

4. Active Tuberculosis (TB): History of active TB within the past year (regardless of treatment status). Exception: Patients with adequately treated past TB (confirmed by standard anti-TB therapy) may be enrolled if >1 year since completion of treatment.

5. Active Autoimmune Diseases:Known or suspected autoimmune disorders (e.g., uveitis, colitis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, hypothyroidism, or asthma requiring bronchodilators).

Exceptions:

Type 1 diabetes mellitus Hypothyroidism managed with hormone replacement Skin conditions not requiring systemic therapy (e.g., vitiligo, psoriasis, alopecia).

6. Interstitial Lung Disease (ILD):

History of ILD or pneumonitis requiring oral/IV steroids within the past year.

7. Immunosuppressive Therapy:

Chronic systemic corticosteroids (≥10 mg prednisone equivalent/day) or other immunosuppressants within 4 weeks prior to enrollment. Inhaled/topical steroids are permitted.

8. Uncontrolled Cardiac Disease: Heart failure (NYHA class ≥2), Unstable angina, Myocardial infarction within the past year, Clinically significant arrhythmias requiring treatment.

9. Pregnancy/Lactation: Pregnant or breastfeeding women (urine/blood pregnancy test required for women of childbearing potential).

10. Concurrent Malignancies:

History of other malignancies except:

Adequately treated non-melanoma skin cancer, Carcinoma in situ of the cervix, Papillary thyroid carcinoma.

11. Hypersensitivity: Known allergy to any component of the study drugs or excipients.

12. Active Infections:

Systemic infections requiring treatment within 1 week prior to enrollment.

Live Vaccines:

13. Administration of live vaccines within 30 days before the first immunotherapy dose.

14. Organ Transplantation: History of allogeneic organ transplantation.

15. Other High-Risk Conditions:

Any condition that may compromise patient safety or compliance per investigator assessment (e.g., severe psychiatric disorders, life-threatening comorbidities, or social/familial risk factors).

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

Sponsors

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Wuhan Union Hospital

Wuhan, Hubei, China

Countries

China

Central Contacts

Chao Wan

Role: CONTACT

wanc@hust.edu.cn

+86 18062775069

Other Identifiers

UNION-NPC-001

Identifier Type: -

Identifier Source: org_study_id