Anlotinib Plus Immunotherapy and Chemoradiotherapy for High-Risk Nasopharyngeal Carcinoma

NCT07385079 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 2025-FXY-257-FLK
• Study Type: interventional
• Target: 412
• Locations: 0 countries
• Sites: N/A

Brief Summary

This trial aimed to evaluate the efficacy of anlotinib hydrochloride combined with benmelstobart, induction chemotherapy, and concurrent chemoradiotherapy (IC+CCRT), versus a regimen of benmelstobart plus IC+CCRT, in patients with high-risk locoregionally advanced nasopharyngeal carcinoma (LANPC).

Conditions

Nasopharyngeal Cancinoma (NPC); Nasopharyngeal Cancer

Keywords

anlotinib hydrochloride; PD-L1 antibody; chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• Failure-free survival (FFS)

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

  3 year

Secondary Outcomes (7)

• Tumor response

  the time of completion of induction chemotherapy, radiotherapy, and adjuvant immunotherapy; from the date of enrollment until the date of the last time that tumorimaging and assessment of disease has been done, assessed up to 62 weeks

• Overall survival (OS)

  3 years

• Distant metastasis-free survival (DMFS)

  3 years

• Locoregional recurrence-free survival (LRRFS)

  3 years

• Adverse events (AEs) and serious adverse events (SAEs)

  3 years

Other Outcomes (3)

• Correlation between pre-treatment PD-L1 expression level and FFS

  3 years

• Evaluate failure-free survival in the subgroup of plasma Epstein-Barr virus DNA level

  3 years

• Evaluate failure-free survival in the subgroup of clinical stage

  3 years

Study Arms (2)

anlotinib hydrochloride Arm

EXPERIMENTAL

Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), and benmelstobart (1200mg, d1) every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Anlotinib hydrochloride (10mg, d1-d14) will be given every 3 weeks for 3 cycles in induction chemotherapy. Subsequently, adjuvant therapy with benmelstobart (1200 mg, d1) will be initiated for a total of 9 cycles.

Drug: Anlotinib Hydrochloride Capsules; Drug: Gemcitabine (GEM); Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy; Drug: Benmelstobart

PD-L1+Chemoradiation Arm

ACTIVE COMPARATOR

Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), and benmelstobart (1200mg, d1) every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Adjuvant therapy with benmelstobart (1200 mg, d1) will be initiated for a total of 9 cycles.

Drug: Gemcitabine (GEM); Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy; Drug: Benmelstobart

Interventions

Anlotinib Hydrochloride Capsules DRUG

Anlotinib hydrochloride (10mg, d1-d14) will be given every 3 weeks for 3 cycles in induction chemotherapy.

anlotinib hydrochloride Arm

Gemcitabine (GEM) DRUG

Gemcitabine 1g/m2, d1 \& 8 of every cycle, every 3 weeks for 3 cycles before radiation.

PD-L1+Chemoradiation Arm; anlotinib hydrochloride Arm

Cisplatin DRUG

Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation

PD-L1+Chemoradiation Arm; anlotinib hydrochloride Arm

Intensity-modulated radiotherapy RADIATION

Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.

PD-L1+Chemoradiation Arm; anlotinib hydrochloride Arm

Benmelstobart DRUG

Benmelstobart 1200mg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 9 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.

PD-L1+Chemoradiation Arm; anlotinib hydrochloride Arm

Eligibility Criteria

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

You may qualify if:

• Age ≥18 and ≤65 years
• Patients with histologically confirmed non-keratinizing nasopharyngeal carcinoma according to WHO criteria.
• Tumor staged as T4N2 and T1-4N3 (AJCC 9th)
• Eastern Cooperative Oncology Group performance score of 0-11.
• Adequate marrow function: white blood cell count \> 4 × 10⁹/L hemoglobin \>90g/L and platelet count \>100×10⁹/L
• Adequate hepatic and renal function：
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×ULN
• Alkaline phosphatase ≤ 2.5 × ULN
• clearance rate ≥ 60 ml/min
• Other laboratory and clinical criteria
• Normal thyroid function, serum amylase and lipase, pituitary hormone levels, inflammatory markers, cardiac enzyme tests and electrocardiogram (ECG)
• For patients aged \>50 years with a history of smoking, normal pulmonary function test (PFT) results are required

You may not qualify if:

• Patients must be informed of the investigational nature of this study and give written informed consent, and be willing and able to comply with the study schedule, including follow-up visits, treatment procedures, laboratory testing, and other protocol-related requirements.
• Women of childbearing potential (WOCBP) must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug (e.g., condoms, physician-guided regular use of oral contraceptives).
• Positive for hepatitis B surface antigen (HBsAg) with hepatitis B virus DNA \>1×103 copies/mL, positive for anti-hepatitis C virus (HCV) antibody , positive for anti-hepatitis C virus (HCV) antibody
• Positive for anti-HIV antibody or diagnosed with acquired immunodeficiency syndrome (AIDS).
• Active pulmonary tuberculosis: Patients with a history of active tuberculosis within the past year should be excluded regardless of treatment status. Patients with a history of active pulmonary tuberculosis more than one year prior should also be excluded, unless they received confirmed and regular anti-tuberculosis treatment.
• Active, known, or suspected autoimmune diseases, including but not limited to uveitis, colitis, hepatitis, hypophysitis, nephritis, vasculitis, systemic lupus erythematosus, hyperthyroidism, hypothyroidism, and asthma requiring bronchodilators. Type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) are allowed.
• History of interstitial lung disease or pneumonia requiring oral or intravenous corticosteroids within the past year; use of vancomycin within the past month.
• Ongoing chronic systemic corticosteroid therapy (equivalent to or greater than prednisone \>10mg per day) or any other immunosuppressive therapy. Patients received inhale or topical corticosteroid are allowed.
• Uncontrolled cardiac conditions, such as:
• Heart failure with New York Heart Association (NYHA) classification ≥ Class II;
• Unstable angina;
• History of myocardial infarction within the past year;
• Supraventricular or ventricular arrhythmias requiring treatment or intervention
• Pregnant or breastfeeding women (pregnancy testing should be considered for women of childbearing potential with active sexual life)
• History or presence of other malignancies, except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma.

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

Study Officials

• Jun Ma, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Ma, M.D.

CONTACT

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

Ya-Qin Wang, Ph. D.

CONTACT

+862087342251; wangyaq@sysucc.org.cn

Study Design

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

Study Record Dates

• First Submitted: September 23, 2025
• First Posted: February 3, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share