QL1706 (PD-1/CTLA-4 Bi-specific Antibody) and Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma.

QL1706 (Iparomlimab and Tuvonralimab Injection,PD-1/ CTLA-4 Bi-specific Antibody) Combined With Chemoradiotherapy Versus Chemoradiotherapy Alone in High-Risk Locoregionally Advanced Nasopharyngeal Carcinoma：A Randomized, Controlled, Multicenter Phase III Clinical Study.

The trial aimed to compare QL1706 combined with induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus IC+CCRT alone in High-risk Locoregionally-Advanced Nasopharyngeal Carcinoma (LANPC).

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Cancer; Nasopharyngeal Cancinoma (NPC)
• Intervention / Treatment: Drug: Gemcitabine; Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy; Drug: QL1706

Detailed Description

The trial plans to enroll patients with stage T4N1and T1-4N2-3 (AJCC 9th) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Patients will be randomized in a 1:1 ratio to receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation or the same regimen plus QL1706 in induction chemotherapy and adjuvant chemotherapy. All patients will receive intensity-modulated radiotherapy (IMRT). QL1706 will begin on day 1 of induction chemotherapy and continue every 3 weeks for 3 cycles in induction therapy and for 9 cycles in adjuvant therapy.

• Study Type: Interventional
• Enrollment (Estimated): 580
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jun Ma, M.D.; Phone Number: +862087343469; Email: majun2@mail.sysu.edu.cn
• Study Contact Backup: Name: Rui Guo, M.D.; Email: guorui@sysucc.org.cn

Study Locations

• China
  • Fujian
    • Fuzhou,, Fujian, China
      • Not yet recruiting
      • Fujian Cancer Hospital
      • Contact: Chuan-Ben Chen
      • Contact: Su-Fang Qiu
  • Guangdong
    • Dongguan, Guangdong, China
      • Not yet recruiting
      • Dongguan People's Hospital
      • Contact: Zhi-Gang Liu
    • FoShan, Guangdong, China
      • Not yet recruiting
      • First People's Hospital of Foshan
      • Contact: Ning Zhang
    • GuangZhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Jun Ma, M.D.; Phone Number: +862087343469; Email: majun2@mail.sysu.edu.cn
    • Guangzhou, Guangdong, China, 510060
      • Not yet recruiting
      • Guangzhou Panyu Central Hospital
      • Contact: Guo-Rong Zou
    • Zhongshan, Guangdong, China
      • Not yet recruiting
      • Zhongshan People's Hospital
      • Contact: Feng Lei
  • Guangxi
    • Nanning, Guangxi, China, 530000
      • Not yet recruiting
      • Cancer Hospital of Guangxi Medical University
      • Contact: Xiao-Dong Zhu, M.D.
  • Guizhou
    • Guiyang, Guizhou, China
      • Not yet recruiting
      • Cancer Hospital of Guizhou Medical University
      • Contact: Feng Jin, M.D.
  • Hubei
    • WuHan, Hubei, China, 430000
      • Not yet recruiting
      • Hubei Province Cancer Hosiptal
      • Contact: De-Sheng Hu, M.D.
    • WuHan, Hubei, China, 430000
      • Not yet recruiting
      • Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
      • Contact: Guang-Yuan Hu, M.D.
    • Wuhan, Hubei, China, 430000
      • Not yet recruiting
      • Renmin Hospital of Wuhan University
      • Contact: Xiang-Pan Li, M.D.
    • Wuhan, Hubei, China, 430000
      • Not yet recruiting
      • Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
      • Contact: Kun-Yu Yang, M.D.
  • Hunan
    • ChangSha, Hunan, China, 410000
      • Not yet recruiting
      • Hunan Cancer Hospital
      • Contact: Ya-Qian Han
    • ChangSha, Hunan, China
      • Not yet recruiting
      • Xiangya Hospital of Central South University
      • Contact: Liang-Fang Shen, M.D.
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Not yet recruiting
      • Jiangsu Cancer Hospital
      • Contact: Xia He, M.D.
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Not yet recruiting
      • The Eye and ENT Hospital of Fudan University
      • Contact: Xiao-Shen Wang, M.D.
  • Sichuan
    • Chengdu, Sichuan, China, 610001
      • Not yet recruiting
      • Sichuan Cancer Hospital
      • Contact: Shi-chuan Zhang, M.D.
  • Tianjin
    • Tianjin, Tianjin, China, 30000
      • Not yet recruiting
      • Tianjin Medical University Cancer Institute & Hospital
      • Contact: Pei-guo Wang, M.D.
  • Xiamen
    • Fujian, Xiamen, China, 361000
      • Not yet recruiting
      • The First Affiliated Hospital of Xiamen University
      • Contact: Qin Lin, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age ≥18 and ≤65 years
2. Patients with histologically confirmed non-keratinizing nasopharyngeal carcinoma according to WHO criteria.

3. Tumor staged as T4N1 and T1-4N2-3 (AJCC 9th)

   • Stage II: T1-3N2
   • Stage III: T1-4N3, T4N1-2
4. Eastern Cooperative Oncology Group performance score of 0-11.
5. Adequate marrow function: white blood cell count > 4 × 10⁹/Lhemoglobin >90g/L and platelet count >100×10⁹/L

6. 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

7. 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
   • For patients with abnormal ECG findings or a prior history of cardiovascular disease (not meeting any exclusion criteria listed in Item 8), additional assessments including myocardial function evaluation and cardiac ultrasound (echocardiography) must be performed, with results within normal limits
8. 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.
9. 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).

Exclusion Criteria

1. 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
2. Positive for anti-HIV antibody or diagnosed with acquired immunodeficiency syndrome (AIDS).
3. 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.
4. 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.
5. Thymic epithelial tumors (TETs), including thymoma, thymic carcinoma, and thymic neuroendocrine tumors (NETTs).
6. History of interstitial lung disease or pneumonia requiring oral or intravenous corticosteroids within the past year; use of vancomycin within the past month.
7. 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.

8. 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
9. Pregnant or breastfeeding women (pregnancy testing should be considered for women of childbearing potential with active sexual life)
10. History or presence of other malignancies, except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma.
11. Known hypersensitivity to macromolecule protein products or any component of QL1706.
12. Active infections requiring systemic treatment within 1 week prior to enrollment.
13. Administration of live vaccines within 30 days prior to the first dose of epalurilimab-tovorolimab.
14. History of organ transplantation or hematopoietic stem cell transplantation.
15. Any other condition assessed by the investigator as potentially compromising patient safety or compliance, such as severe illnesses requiring urgent treatment (including psychiatric disorders), significantly abnormal laboratory values, or other psychological, familial, or social risk factors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QL1706 Arm; Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), 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. QL1706 5mg/kg 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.	Drug: Gemcitabine; Gemcitabine 1g/m2, d1 & 8 of every cycle, every 3 weeks for 3 cycles before radiation.; Drug: Cisplatin; Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation; Radiation: Intensity-modulated radiotherapy; Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.; Drug: QL1706; QL1706 5mg/kg 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.
Active Comparator: Chemoradiation Arm; Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), 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.	Drug: Gemcitabine; Gemcitabine 1g/m2, d1 & 8 of every cycle, every 3 weeks for 3 cycles before radiation.; Drug: Cisplatin; Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation; Radiation: Intensity-modulated radiotherapy; Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure-free survival (FFS) in intention-to-treat population	Multiple endpoint 1: calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.	3 years
Overall survival (OS) in intention-to-treat population	Multiple endpoint 2: calculated from randomization to the date of death from any cause.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs) and serious adverse events (SAEs)	Graded according to CTCAE V5.0.	3 years
Distant metastasis-free survival (DMFS)	calculated from randomization to the date of first distant metastasis.	3 years
Locoregional recurrence-free survival (LRRFS)	calculated from randomization to the date of locoregional persistence or 1st locoregional recurrence.	3 years
Failure-free survival (FFS) within different subgroups	analyses for FFS will be performed within the following subgroups: Epstein-Barr virus (EBV) DNA (≤4000copies/ml vs. >4000copies/ml), different PD-L1 expression levels, age, gender, performance status, T category, N category, and stage (III vs. IVA).	3 years
Failure-free survival (FFS) in per-protocol population	calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.	3 years
Overall survival (OS) in per-protocol population	calculated from randomization to the date of death from any cause.	3 years
Quality of life (QoL)	The change of QoL from randomization to the start of radiotherapy, the end of radiotherapy, 13-16 weeks after radiotherapy, 2 years and 3 years after randomization. The EORTC QoL questionnaire-C30 (EORTC QLQ-C30）version 3.0 will be used. This questionnaire comprises 30 questions, 24 of which are aggregated into nine multi-question scales, that is, five functioning scales (e.g., physical), three symptom scales (e.g., fatigue) and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual.	week 1, 20, 40, 64
Tumor response	Evaluation of tumor response as CR, PR, SD, PD, NA by clinicians	Every 6 weeks（the time of completion of induction chemotherapy, radiotherapy, and adjuvnt 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 74 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between pre-treatment PD-L1 expression level and FFS	Pre-treatment PD-L1 expression level of tumor cell is evaluated centrally by means of immunohistochemical testing.	3 years
Evaluate failure-free survival in the subgroup of plasma Epstein-Barr virus DNA level	Subgroup analysis	3 years
Evaluate failure-free survival in the subgroup of clinical stage	Subgroup analysis	3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Qilu Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jun Ma, M.D., Sun Yat-sen University

Publications and helpful links

General Publications

• 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.
• 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.
• Zhao Y, Ma Y, Zang A, Cheng Y, Zhang Y, Wang X, Chen Z, Qu S, He J, Chen C, Jin C, Zhu D, Li Q, Liu X, Su W, Ba Y, Hao Y, Chen J, Zhang G, Qu S, Li Y, Feng W, Yang M, Liu B, Ouyang W, Liang J, Yu Z, Kang X, Xue S, Yang G, Yan W, Yang Y, Liu Z, Peng Y, Fanslow B, Huang X, Zhang L, Zhao H. First-in-human phase I/Ib study of QL1706 (PSB205), a bifunctional PD1/CTLA4 dual blocker, in patients with advanced solid tumors. J Hematol Oncol. 2023 May 8;16(1):50. doi: 10.1186/s13045-023-01445-1.

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 19, 2024
• First Submitted That Met QC Criteria: December 23, 2024
• First Posted (Actual): December 27, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Chemoradiotherapy; PD-1/CTLA-4 Bi-specific Antibody
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Gemcitabine
• Other Study ID Numbers: 2024-FXY-409-FLK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Complete de-identified patient data set will be submitted onto an online platform.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No