Ivonescimab Combined With Chemoradiotherapy in High-Risk Locoregionally Advanced Nasopharyngeal Carcinoma

Official title

Ivonescimab Combined With Chemoradiotherapy in High-Risk Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II, Multicenter, Single-Arm Clinical Trial

Overview

This trial aims to study the role of Ivonescimab combined with chemoradiotherapy in high-Risk locoregionally advanced nasopharyngeal carcinoma.

Detailed description

The trial plans to enroll patients with T3N2M0+ Stage III (AJCC 9th) locoregionally advanced nasopharyngeal carcinoma (LANPC). Patients will receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin combined with ivonescimab, followed by concurrent chemoradiotherapy with cisplatin, and then 9 cycles of adjuvant ivonescimab. Ivonescimab will be administered every 3 weeks starting from day 1 of induction therapy and continued through the adjuvant phase.

Interventions

• Drug Ivonescimab（AK112，a PD-1/VEGF bispecific antibody）
  Ivonescimab (AK112) is a novel PD-1/VEGF bispecific antibody designed to simultaneously block PD-1-mediated immune evasion and inhibit VEGF-driven angiogenesis. In this study, ivonescimab is administered intravenously at a dose of 10 mg/kg every 3 weeks, starting on Day 1 of induction chemotherapy (3 cycles), followed by concurrent chemoradiotherapy (no ivonescimab), and then continued as adjuvant monotherapy for 9 additional cycles.

Primary outcome measures

• Complete response rate (CRR) [Time frame: At the end of induction therapy]

Secondary outcome measures (7)

• Objective response rate (ORR) [Time frame: At the end of induction therapy]
• Failure-free survival (FFS) [Time frame: 2 years]
• Overall survival (OS) [Time frame: 2 years]
• Distant metastasis-free survival (DMFS) [Time frame: 2 years]
• Locoregional recurrence-free survival (LRRFS) [Time frame: 2 years]
• Adverse events (AEs) and serious adverse events (SAEs) [Time frame: 2 years]
• Quality of life (QoL) [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Age between 18 and 65 years.
• Histologically confirmed non-keratinizing carcinoma (according to WHO classification).
• ECOG performance status of 0 or 1.
• Previously untreated nasopharyngeal carcinoma staged as T3N2M0 or Stage III according to the AJCC 9th edition.
• Adequate bone marrow function, defined as white blood cell count > 4×10⁹/L, hemoglobin > 90 g/L, and platelet count > 100×10⁹/L.
• Adequate liver and renal function, defined as total bilirubin ≤ 1.5 × ULN; AST and/or ALT ≤ 2.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; and creatinine clearance ≥ 60 mL/min.
• Normal thyroid function, amylase, lipase, pituitary function, inflammatory markers, myocardial enzymes, and ECG. For patients over 50 years old with a smoking history, pulmonary function test results must be normal. For patients with ECG abnormalities or a cardiovascular history not meeting exclusion criteria #8, echocardiography and cardiac function tests must be normal.
• Signed informed consent and willingness to comply with all scheduled visits, treatment procedures, laboratory tests, and other study-related requirements.
• Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to use reliable contraception from screening until 1 year after completion of treatment.

Exclusion criteria

• Tumor invasion of major blood vessels or significant recent (within 1 month) nasopharyngeal or nasal bleeding (>5 mL).
• HBsAg positive with HBV DNA > 1×10³ copies/mL, or anti-HCV antibody positive.
• HIV antibody positive or diagnosed with AIDS.
• Active tuberculosis or history of active tuberculosis within the past year, unless adequately treated.
• Active, known, or suspected autoimmune disease, including but not limited to uveitis, colitis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, hypothyroidism, or asthma requiring bronchodilator therapy; exceptions include type 1 diabetes, hypothyroidism requiring hormone replacement, and localized skin conditions not requiring systemic therapy (e.g., vitiligo, psoriasis, or alopecia).
• History of interstitial lung disease or pneumonitis requiring corticosteroid treatment within the past year.
• Chronic systemic corticosteroid therapy (≥10 mg/day prednisone or equivalent) or use of other immunosuppressive therapy; inhaled or topical corticosteroids are allowed.
• Uncontrolled cardiovascular disease, including NYHA Class ≥ 2 heart failure, unstable angina, myocardial infarction within 1 year, or supraventricular/ventricular arrhythmias requiring intervention.
• Pregnant or breastfeeding women; pregnancy testing is required for women of childbearing potential.
• History or presence of other malignancies, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or papillary thyroid carcinoma.
• Known hypersensitivity to monoclonal antibodies or any component of ivonescimab.
• Active systemic infection requiring treatment within 1 week before study treatment.
• Receipt of live vaccine within 30 days prior to the first dose of ivonescimab.
• History of organ transplantation.
• History of psychiatric illness, substance abuse, alcohol or drug dependence.
• Any other condition which, in the opinion of the investigator, could compromise patient safety or compliance with the study protocol, including severe uncontrolled comorbidities, serious abnormal lab findings, or psychosocial risk factors.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 3 centers

• The First Affiliated Hospital of Xiamen University — Xiamen
• Sun Yat-sen University Cancer Center — Guangzhou
• The Affiliated Hospital of Guilin Medical University — Guilin

Publications

• Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter rando PMID 34341578
• Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced PMID 27686945
• Chen BJ, Chapuy B, Ouyang J, Sun HH, Roemer MG, Xu ML, Yu H, Fletcher CD, Freeman GJ, Shipp MA, Rodig SJ. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2013 Jul 1;19(13):3462-73. doi: 10.1158/1078-0432.CCR-13-0855. Epub 2013 May 14. PMID 23674495
• Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24. PMID 28837405
• Wang J, Zhou C, Yao W, Wang Q, Min X, Chen G, Xu X, Li X, Xu F, Fang Y, Yang R, Yu G, Gong Y, Zhao J, Fan Y, Liu Q, Cao L, Yao Y, Liu Y, Li X, Wu J, He Z, Lu K, Jiang L, Hu C, Zhao W, Zhang B, Shi W, Zhang X, Cheng Y; CAPSTONE-1 Study Group. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomis PMID 35576956
• Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induct PMID 31150573

Identifiers

NCT: NCT07064902 · 2025-FXY-113-FLK

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗