PD-1 Blockade Combined With De-intensified Chemoradiotherapy Sparing Concurrent Cisplatin in Nasopharyngeal Carcinoma

NCT04907370 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: JS001-ISS-CO291
• Study Type: interventional
• Target: 532
• Locations: 1 country
• Sites: 12

Brief Summary

This is a phase 3, multi-center, randomized controlled trial, with the purpose to evaluate the therapeutic efficacy and safety of PD-1 blockade (toripalimab) combined with the de-intensified chemoradiotherapy sparing concurrent cisplatin (i.e., toripalimab incorporated into induction chemotherapy and radiotherapy) in high-risk locoregionally advanced nasopharyngeal carcinoma.

Conditions

Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal Carcinoma; Immune checkpoint inhibitor; Radiotherapy; Concurrent cisplatin

Outcome Measures

Primary Outcomes (2)

• Failure-free survival (FFS)

  Failure-free survival is measured from day of diagnosis until treatment failure, death from any cause, or last follow-up visit, whichever occurred first

  3-year

• Incidence rate of all-grade vomiting

  Incidence rate of all-grade vomiting during treatment assessed by clinicians according to the Common Terminology Criteria for Adverse Events 5.0.

  Through study completion, an average of 1 year

Secondary Outcomes (7)

• Overall survival (OS)

  3-year

• Locoregional failure-free survival (LRFFS)

  3-year

• Distant failure-free survival (DFFS)

  3-year

• Incidence rate of investigator-reported adverse events (AEs)

  3-year

• Incidence rate of patient-reported adverse events (AEs)

  3-year

Other Outcomes (10)

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

  3-year

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

  3-year

• Correlation between the percentage of tumor-infiltrating lymphocytes (TILs) and PFS

  3-year

Study Arms (2)

Toripalimab Combined with Induction Chemotherapy Followed by Radiotherapy Alone

EXPERIMENTAL

All participants will receive induction chemotherapy (IC; every 3 weeks × 3 cycles; gemcitabine 1000 mg/m2 day 1, 8 + cisplatin 80 mg/m2 day 1) followed by intensity-modulated radiotherapy (IMRT; 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day) alone. PD-1 blockade toripalimab (240 mg per cycle) will start on day 1 of the first cycle IC and continue every 3 weeks for 6 cycles till the end of IMRT, involving the whole-course of IC + IMRT alone. The first and last 3 cycles of toripalimab are administrated concurrently with IC and IMRT, respectively. After 3 weeks of the completion of IMRT, adjuvant toripalimab (240 mg per cycle) will begin every 3 weeks for 11 cycles.

Drug: PD-1 blocking antibody; Drug: Gemcitabine; Drug: Cisplatin (80mg/m2); Radiation: Intensity-modulated radiotherapy

Toripalimab Combined with Induction Chemotherapy Followed by Concurrent Chemoradiotherapy

ACTIVE COMPARATOR

All participants will receive induction chemotherapy (IC; every 3 weeks × 3 cycles of gemcitabine 1000 mg/m2 day 1, 8 + cisplatin 80 mg/m2 day 1) followed by concurrent chemoradiotherapy (CCRT; every 3 weeks × 2 cycles of cisplatin + IMRT 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day). PD-1 blockade toripalimab (240 mg per cycle) will start on day 1 of the first cycle IC and continue every 3 weeks for 6 cycles till the end of CCRT, involving the whole-course of IC + CCRT. The first and last 3 cycles of toripalimab are administrated concurrently with IC and CCRT, respectively. After 3 weeks of the completion of CCRT, adjuvant toripalimab (240 mg per cycle) will begin every 3 weeks for 11 cycles.

Drug: PD-1 blocking antibody; Drug: Gemcitabine; Drug: Cisplatin (80mg/m2); Drug: Cisplatin (100mg/m2); Radiation: Intensity-modulated radiotherapy

Interventions

PD-1 blocking antibody DRUG

1. IC phase of PD-1 blocking antibody: every 3 weeks × 3 cycles; 240 mg, day 1; start on day 1 of the first cycle IC and continue every 3 weeks for 3 cycles till the end of IC. 2. IMRT phase of PD-1 blocking antibody: every 3 weeks × 3 cycles; 240 mg, day 1; start on day 1 of IMRT or CCRT and continue every 3 weeks for 3 cycles till the end of IMRT. 3. Adjuvant PD-1 blocking antibody: every 3 weeks × 11 cycles; 240 mg, day 1

Also known as: PD-1 Blockade

Toripalimab Combined with Induction Chemotherapy Followed by Concurrent Chemoradiotherapy; Toripalimab Combined with Induction Chemotherapy Followed by Radiotherapy Alone

Gemcitabine DRUG

Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3 cycles

Also known as: GEM

Toripalimab Combined with Induction Chemotherapy Followed by Concurrent Chemoradiotherapy; Toripalimab Combined with Induction Chemotherapy Followed by Radiotherapy Alone

Cisplatin (80mg/m2) DRUG

Cisplatin as induction chemotherapy, 80 mg/m2 day 1 per cycle, every 3 weeks for 3 cycles

Also known as: DDP

Toripalimab Combined with Induction Chemotherapy Followed by Concurrent Chemoradiotherapy; Toripalimab Combined with Induction Chemotherapy Followed by Radiotherapy Alone

Cisplatin (100mg/m2) DRUG

Cisplatin as concurrent chemotherapy, 100 mg/m2 day 1 per cycle, every 3 weeks for 2 cycles

Also known as: DDP

Toripalimab Combined with Induction Chemotherapy Followed by Concurrent Chemoradiotherapy

Intensity-modulated radiotherapy RADIATION

Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day

Also known as: IMRT

Toripalimab Combined with Induction Chemotherapy Followed by Concurrent Chemoradiotherapy; Toripalimab Combined with Induction Chemotherapy Followed by Radiotherapy Alone

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 to 65;
• Pathological type: non-keratinizing carcinoma (World Health Organization criteria);
• Diagnosed with LANPC (T4N1, T1-4N2-3) according to the 8th edition clinical staging system of the American Joint Committee on Cancer \[AJCC\]/Union for International Cancer Control \[UICC\];
• ECOG performance score: 0 to 1;
• Normal bone marrow function: white blood cell count \> 4×109/L, hemoglobin \> 90g/L, platelet count \> 100×109/L;

You may not qualify if:

• Normal liver and kidney function: total bilirubin ≤ 1.5 × upper limit of normal (ULN); alanine transaminase and aspartate transaminase ≤ 2.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; creatinine clearance rate ≥ 60 ml/min;
• Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule;
• Subjects with pregnancy ability must agree to use reliable contraceptive measures from screening to 1 year after treatment.
• Hepatitis B virus surface antigen (HBsAg) positive and HBV DNA \> 1×10E3 copies/ml; anti-hepatitis C virus positive;
• Anti-human immunodeficiency virus (HIV) positive or diagnosed with acquired immune deficiency syndrome (AIDS);
• Active tuberculosis: active tuberculosis in the past 1 year should be excluded regardless with treatment; history of active tuberculosis over 1 year should be excluded except that previous regulatory anti-tuberculosis treatment is proved;
• Active, known or suspected autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma requiring bronchiectasis). Exceptions are type I diabetes mellitus, hypothyroidism requiring hormone replacement therapy, skin disorders requiring no systemic treatment (such as vitiligo, psoriasis or alopecia);
• Previous interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy;
• Chronic treatment with systemic glucocorticoid (dose equivalent to or over 10 mg prednisone per day) or any other form of immunosuppressive therapy. Subjects who used inhaled or topical corticosteroids were eligible;
• Uncontrolled heart disease, for example: 1) heart failure (NYHA level ≥ 2); 2) unstable angina; 3) myocardial infarction in past 1 year; 4) supraventricular or ventricular arrhythmia requiring treatment or intervention;
• Pregnant or lactating women (pregnancy test should be considered for women with sexual life and fertility);
• Previous or concurrent with other malignant tumors, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer;
• Allergy to macromolecular protein preparations, or any component of nivolumab;
• Active infection requiring systemic treatment;
• Receiving live vaccine within 30 days of the initial nivolumab;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (12)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Location

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality, China

Location

First People's Hospital of Foshan

Foshan, Guangdong, China

Location

Panyu central hospital

Guangzhou, Guangdong, 510060, China

Location

Cancer Hospital of Guangxi Medical University

Nanning, Guangxi, China

Location

Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, China

Location

Hubei Province Cancer Hosiptal

Wuhan, Hubei, China

Location

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

Wuhan, Hubei, China

Location

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

Wuhan, Hubei, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, China

Location

Jiangxi Province Cancer Hospital

Nanchang, Jiangxi, China

Location

Zhejiang Province Cancer Hospital

Hangzhou, Zhejiang, China

Location

Related Publications (6)

• 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 RESULT

• Ma BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, Foster NR, Riess JW, Agulnik M, Chang AYC, Chopra A, Kish JA, Chung CH, Adkins DR, Cullen KJ, Gitlitz BJ, Lim DW, To KF, Chan KCA, Lo YMD, King AD, Erlichman C, Yin J, Costello BA, Chan ATC. Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). J Clin Oncol. 2018 May 10;36(14):1412-1418. doi: 10.1200/JCO.2017.77.0388. Epub 2018 Mar 27.

  PMID: 29584545 RESULT

• 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 RESULT

• Fang W, Yang Y, Ma Y, Hong S, Lin L, He X, Xiong J, Li P, Zhao H, Huang Y, Zhang Y, Chen L, Zhou N, Zhao Y, Hou X, Yang Q, Zhang L. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 2018 Oct;19(10):1338-1350. doi: 10.1016/S1470-2045(18)30495-9. Epub 2018 Sep 10.

  PMID: 30213452 RESULT

• Wang FH, Wei XL, Feng J, Li Q, Xu N, Hu XC, Liao W, Jiang Y, Lin XY, Zhang QY, Yuan XL, Huang HX, Chen Y, Dai GH, Shi JH, Shen L, Yang SJ, Shu YQ, Liu YP, Wang W, Wu H, Feng H, Yao S, Xu RH. Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02). J Clin Oncol. 2021 Mar 1;39(7):704-712. doi: 10.1200/JCO.20.02712. Epub 2021 Jan 25.

  PMID: 33492986 RESULT

• DIAMOND Study Group; Xu C, Liang XY, Huang XQ, Jin F, Yang KY, Hu GY, Zhu XD, Wang Y, Huang Y, Zhang N, Hu DS, Guo L, Zou GR, Chen XZ, Xiao SW, Li JG, Shen LF, Li YY, Huang J, Long GX, Li L, Huang L, She LJ, Wu Y, Zeng WH, Qiang MY, Liu WX, Su Y, Tang LL, Xie FY, Han F, Lu LX, Xiang YQ, Mao YP, Li WF, Liu X, Yang Q, Zhou GQ, Guo R, Ouyang PY, Wang XH, Chen L, Liu LT, Lin L, Li JB, Lin AH, Zhao HY, Hong SB, Jie YS, Huang HL, Tang XH, Zeng YC, Yun JP, Zang SB, Du ZM, Ye ZL, Liu LZ, Tian L, Li HJ, Peng YL, Liu N, Li YQ, Liang YL, Wei HM, Chen YP, Zhang Y, Du XJ, Lv JW, Sun Y, Ma J. Toripalimab Combination Therapy Without Concurrent Cisplatin for Nasopharyngeal Carcinoma: The DIAMOND Randomized Clinical Trial. JAMA. 2025 Sep 16;334(11):973-983. doi: 10.1001/jama.2025.13205.

  PMID: 40839372 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Immune Checkpoint Inhibitors; Gemcitabine; Cisplatin; Radiotherapy, Intensity-Modulated

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

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; 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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President of SYSUCC

Study Record Dates

• First Submitted: May 26, 2021
• First Posted: May 28, 2021
• Study Start: August 1, 2021
• Primary Completion: March 1, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (12)