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

NCT07064902 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2025-FXY-113-FLK
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Nasopharyngeal Carcinoma (NPC)

Keywords

PD-1/VEGF bispecific antibody; Chemoradiotherapy; Anti-PD-1 Therapy; Ivonescimab; Immunotherapy; Bispecific Antibody

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CRR)

  Disappearance of all target lesions, with all pathological lymph nodes (including both target and non-target nodes) reduced in short axis to less than 10 mm.

  At the end of induction therapy

Secondary Outcomes (7)

• Objective response rate (ORR)

  At the end of induction therapy

• Failure-free survival (FFS)

  2 years

• Overall survival (OS)

  2 years

• Distant metastasis-free survival (DMFS)

  2 years

• Locoregional recurrence-free survival (LRRFS)

  2 years

Study Arms (1)

Ivonescimab arm

EXPERIMENTAL

Participants in this arm will receive induction chemotherapy with gemcitabine (1000 mg/m² on Days 1 and 8, Q3W × 3 cycles) and cisplatin (80 mg/m² on Day 1, Q3W × 3 cycles), combined with ivonescimab (10 mg/kg on Day 1, Q3W × 3 cycles). This will be followed by concurrent chemoradiotherapy (IMRT, 70 Gy/33 fractions, with cisplatin 100 mg/m² on Day 1, Q3W × 2 cycles), and then adjuvant ivonescimab monotherapy (10 mg/kg Q3W × 9 cycles).

Drug: Ivonescimab（AK112，a PD-1/VEGF bispecific antibody）

Interventions

Ivonescimab（AK112，a PD-1/VEGF bispecific antibody） DRUG

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.

Ivonescimab 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 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (3)

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

The Affiliated Hospital of Guilin Medical University

Guilin, Guangxi, 541001, China

Location

Related Publications (6)

• 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 randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 2.

  PMID: 34341578 BACKGROUND

• 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 nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Nov;17(11):1509-1520. doi: 10.1016/S1470-2045(16)30410-7. Epub 2016 Sep 27.

  PMID: 27686945 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Jun;23(6):739-747. doi: 10.1016/S1470-2045(22)00224-8. Epub 2022 May 13.

  PMID: 35576956 BACKGROUND

• 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 Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.

  PMID: 31150573 BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

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

Lei Chen, M.D.

CONTACT

chenlei@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 7, 2025
• First Posted: July 15, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)