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

NCT06749899 | Recruiting Phase 3 DMC

• 1 other identifier: 2024-FXY-409-FLK
• Study Type: interventional
• Target: 580
• Locations: 1 country
• Sites: 19

Brief Summary

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).

Conditions

Nasopharyngeal Cancinoma (NPC); Nasopharyngeal Cancer

Keywords

Immunotherapy; PD-1/CTLA-4 Bi-specific Antibody; Chemoradiotherapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Failure-free survival (FFS) in per-protocol population

  3 years

• Overall survival (OS) in per-protocol population

  3 years

• Locoregional recurrence-free survival (LRRFS)

  3 years

• Distant metastasis-free survival (DMFS)

  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)

QL1706 Arm

EXPERIMENTAL

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: QL1706; Drug: Gemcitabine; Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy

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), 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; Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy

Interventions

QL1706 DRUG

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.

QL1706 Arm

Gemcitabine DRUG

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

Chemoradiation Arm; QL1706 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

Chemoradiation Arm; QL1706 Arm

Intensity-modulated radiotherapy RADIATION

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

Chemoradiation Arm; QL1706 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 T4N1 and T1-4N2-3 (AJCC 9th)
• Stage II: T1-3N2
• Stage III: T1-4N3, T4N1-2
• Eastern Cooperative Oncology Group performance score of 0-11.
• Adequate marrow function: white blood cell count \> 4 × 10⁹/Lhemoglobin \>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.
• Thymic epithelial tumors (TETs), including thymoma, thymic carcinoma, and thymic neuroendocrine tumors (NETTs).
• 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)

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Qilu Pharmaceutical Co., Ltd.: collaborator

Study Sites (19)

Fujian Cancer Hospital

Fuzhou, Fujian, China

NOT YET RECRUITING

Dongguan People's Hospital

Dongguan, Guangdong, China

NOT YET RECRUITING

First People's Hospital of Foshan

Foshan, Guangdong, China

NOT YET RECRUITING

Guangzhou Panyu Central Hospital

Guangzhou, Guangdong, 510060, China

NOT YET RECRUITING

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Zhongshan People's Hospital

Zhongshan, Guangdong, China

NOT YET RECRUITING

Cancer Hospital of Guangxi Medical University

Nanning, Guangxi, 530000, China

NOT YET RECRUITING

Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, China

NOT YET RECRUITING

Hubei Province Cancer Hosiptal

Wuhan, Hubei, 430000, China

NOT YET RECRUITING

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430000, China

NOT YET RECRUITING

Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

NOT YET RECRUITING

Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

NOT YET RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410000, China

NOT YET RECRUITING

Xiangya Hospital of Central South University

Changsha, Hunan, China

NOT YET RECRUITING

Jiangsu Cancer Hospital

Nanjing, Jiangsu, 210000, China

NOT YET RECRUITING

The Eye and ENT Hospital of Fudan University

Shanghai, Shanghai Municipality, 200000, China

NOT YET RECRUITING

Sichuan Cancer Hospital

Chengdu, Sichuan, 610001, China

NOT YET RECRUITING

Tianjin Medical University Cancer Institute ＆ Hospital

Tianjin, Tianjin Municipality, 30000, China

NOT YET RECRUITING

The First Affiliated Hospital of Xiamen University

Fujian, Xiamen, 361000, China

NOT YET RECRUITING

Related Publications (3)

• 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

• 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.

  PMID: 37158938 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 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

Rui Guo, M.D.

CONTACT

guorui@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: December 19, 2024
• First Posted: December 27, 2024
• Study Start: May 4, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 22, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (19)