LDRT Combined With Toripalimab and Chemotherapy for Recurrent/Metastatic NPC (LIGHT)

Low-dose Radiotherapy (LDRT) Combined With Toripalimab and GP Chemotherapy for Recurrent/Metastatic Nasopharyngeal Carcinoma (LIGHT): A Multicentre, Open-Label, Single-Arm Phase II Clinical Study

This study aims to evaluate the efficacy and safety of LDRT combined with toripalimab and GP chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma through a prospective, open-label, single-arm Phase II clinical trial.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Cancinoma (NPC); Nasopharangeal Cancer
• Intervention / Treatment: Drug: Gemcitabine(GEM); Drug: Cisplatin; Drug: Toripalimab; Radiation: LDRT

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jun Ma, M.D.; Phone Number: +862087343469; Email: majun2@mail.sysu.edu.cn
• Study Contact Backup: Name: Zhe Li, Ph.D.; Phone Number: +862087342370; Email: lizhe2@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Jun Ma, vice president; Phone Number: +862087343469; Email: majun2@mail.sysu.edu.cn
      • Principal Investigator: Jun Ma, Professor
    • Shenzhen, Guangdong, China, 518116
      • Recruiting
      • Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
      • Contact: Yan-Ling Wu; Phone Number: 0755-66618168; Email: wuyl1202@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age: 18-65 years old.
• Histologically confirmed non-keratinizing nasopharyngeal carcinoma (WHO Type II or III).
• ECOG Performance Status score of 0-1.
• At least one measurable lesion as per RECIST v1.1 criteria.
• Patients with newly diagnosed metastatic NPC, or patients with locoregionally advanced NPC who developed metastasis ≥6 months or recurrence ≥12 months after completing radical radiotherapy/chemotherapy for the primary lesion.
• No prior radiotherapy, chemotherapy, immunotherapy, or biological therapy for recurrent/metastatic lesions.

• Adequate organ function, meeting the following criteria within 7 days prior to treatment:

  1. Hematological criteria (without transfusion or hematopoietic growth factor support within 14 days):

     1. Hemoglobin (Hb) ≥90 g/L.
     2. White Blood Cell (WBC) count ≥4.0 × 10⁹/L.
     3. Platelet count (PLT) ≥100 × 10⁹/L.

  2. Biochemical criteria:

     1. Total Bilirubin (TBIL) ≤1.5 × Upper Limit of Normal (ULN).
     2. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5 × ULN.
     3. Serum Creatinine (Cr) ≤1.5 × ULN AND Creatinine Clearance (CCr) ≥60 mL/min.
  3. Coagulation function: INR and APTT ≤1.5 × ULN.
  4. Normal results for myocardial injury markers, heart failure markers, and electrocardiogram (ECG). For patients with abnormal results in any of these, the investigator will assess the need for Doppler echocardiography.
  5. Thyroid function: TSH ≤ ULN. If abnormal, FT3 and FT4 levels should be considered; patients can be enrolled if FT3 and FT4 levels are normal.
• Women of childbearing potential must have used reliable contraception, have a negative serum pregnancy test within 7 days before enrollment, and be willing to use adequate contraception during the trial and for 8 weeks after the last dose of the study drug, or be surgically sterile. Men must agree to use adequate contraception or be surgically sterile during the trial and for 8 weeks after the last dose.
• Voluntary provision of signed informed consent, with good compliance.

Exclusion Criteria:

• Disease progression within 6 months after completing standard treatment for locoregionally advanced nasopharyngeal carcinoma.
• Absence of identifiable tumor lesions in both the primary site and locoregional lymph nodes, precluding the development of an LDRT plan.
• Inability to undergo MRI due to reasons such as implanted metal devices or claustrophobia.
• Requirement for systemic use of corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose or during the study. Inhaled or topical steroids and adrenal replacement steroid doses >10 mg/day prednisone equivalent are permitted in the absence of active autoimmune disease. Physiological replacement doses of corticosteroids (≤10 mg/day prednisone equivalent) are allowed.
• Recurrent target lesions suitable for curative surgery or a second course of radiotherapy.
• History of any active autoimmune or autoimmune disease, or known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. Exceptions include type I diabetes, hypothyroidism requiring hormone replacement therapy, and skin disorders not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
• Active or uncontrolled severe infection (≥CTCAE Grade 3) within 4 weeks prior to enrollment.
• History of active tuberculosis within the past year, regardless of treatment. Patients with a history of active pulmonary tuberculosis over 1 year ago who have documented evidence of adequate past anti-tuberculosis treatment may be considered; otherwise, they are excluded.
• History of hypertension that cannot be adequately controlled with a single antihypertensive medication (systolic BP ≥150 mmHg or diastolic BP ≥90 mmHg).
• Clinically significant bleeding symptoms or definite bleeding tendency, specifically excluding cases of local recurrence with high bleeding risk or cases within 1 year post-radiotherapy assessed to have a high risk of necrosis.
• Urinalysis showing urine protein ≥ ++ AND confirmed 24-hour urine protein ≥1.0 g.
• Myocardial ischemia (above Grade I), myocardial infarction, arrhythmia (including QTc ≥480 ms), or ≥ Grade 2 congestive heart failure (NYHA classification) within 6 months prior to enrollment.
• If an echocardiogram is required per Inclusion Criterion 7(4), results showing Left Ventricular Ejection Fraction (LVEF) below the lower limit of normal (60%).
• Diagnosis of other malignancies within 5 years prior to enrollment, except for cured non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma.
• Presence of leptomeningeal or central nervous system metastases.
• HIV positive, TP positive, liver cirrhosis, decompensated liver disease, active hepatitis (uncontrolled active hepatitis despite treatment: Hepatitis B - HBsAg positive and HBV DNA ≥1 × 10⁴ copies/mL; Hepatitis C - HCV RNA positive with abnormal liver function; co-infection with HBV and HCV) requiring antiviral therapy.
• Participation in another anti-tumor drug clinical trial within 4 weeks prior to enrollment.
• Administration of any live attenuated vaccine within 30 days prior to enrollment.
• Contraindications to radiotherapy.
• Known allergy to the study drug or any of its excipients, or history of severe allergic reactions to other monoclonal antibodies.
• History of psychoactive drug abuse unable to be abstained, or presence of psychiatric disorders.
• Any other condition assessed by the investigator as potentially endangering the patient's safety or compliance, including severe concurrent diseases (including psychiatric disorders) requiring prompt treatment, severely abnormal laboratory test results, or other psychological, familial, or sociological factors deemed high-risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LDRT + Toripalimab + GP chemotherapy; Patients will receive LDRT plus toripalimab and GP chemotherapy for 4-6 cycles, then followed by toripalimab until disease progression or unacceptable toxicity.

Drug: Gemcitabine(GEM); Gemcitabine 1000mg/m2, d1 & 8 of every cycle, every 3 weeks for 4-6 cycles; Drug: Cisplatin; Cisplatin 80mg/m2, d1 of every cycle, every 3 weeks for 4-6 cycles; Drug: Toripalimab; Toripalimab 240 mg, d1of every cycle, every 3 weeks for 4-6 cycles. Toripalimab maintenance, 240 mg, d1of every cycle, every 3 weeks until disease progression or unacceptable toxicity.; Radiation: LDRT; Irradiation of the primary lesion and regional metastatic lymph nodes, 0.5 Gy per fraction for 4 fractions, d0-3, every 3 weeks for 4-6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) assessed by RECIST 1.1	PFS was defined as the time from enrollment to the first occurrence of disease progression as determined according to RECIST v1.1 or death from any cause, whichever occurs first.	up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate（ORR）	The proportion of patients who achieved a complete response (CR) or partial response (PR), assessed according to RECIST v1.1.	up to approximately 2 years
Progression-free survival (PFS) assessed by iRECIST	PFS was defined as the time from enrollment to the first occurrence of disease progression as determined according to iRECIST or death from any cause, whichever occurs first.	up to approximately 2 years
Overall survival (OS)	OS was defined as the time from enrollment to death from any cause.	up to approximately 4 years
Adverse events	All adverse event or serious adverse event that occurred during the study period according to CTCAE V5.0.	up to approximately 2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Jun Ma, M.D., Sun Yat-sen University

Publications and helpful links

General Publications

• 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.
• Chen YP, Chan ATC, Le QT, Blanchard P, Sun Y, Ma J. Nasopharyngeal carcinoma. Lancet. 2019 Jul 6;394(10192):64-80. doi: 10.1016/S0140-6736(19)30956-0. Epub 2019 Jun 6.
• Lee N, Harris J, Garden AS, Straube W, Glisson B, Xia P, Bosch W, Morrison WH, Quivey J, Thorstad W, Jones C, Ang KK. Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial 0225. J Clin Oncol. 2009 Aug 1;27(22):3684-90. doi: 10.1200/JCO.2008.19.9109. Epub 2009 Jun 29.
• Wang H, Yao Z, Kang K, Zhou L, Xiu W, Sun J, Xie C, Yu M, Li Y, Zhang Y, Zheng Y, Lin G, Pan X, Wu Y, Luo R, Wang L, Tang M, Liao S, Zhu J, Zhou X, Zhang X, Xu Y, Liu Y, Peng F, Wang J, Xiang L, Yin L, Deng L, Huang M, Gong Y, Zou B, Wang H, Wu L, Yuan Z, Bi N, Fan M, Xu Y, Tong R, Yi L, Gan L, Xue J, Mo X, Chen C, Na F, Lu Y. Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer. Med. 2024 Oct 11;5(10):1237-1254.e9. doi: 10.1016/j.medj.2024.06.002. Epub 2024 Jul 3.
• Lee NY, Zhang Q, Pfister DG, Kim J, Garden AS, Mechalakos J, Hu K, Le QT, Colevas AD, Glisson BS, Chan AT, Ang KK. Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial. Lancet Oncol. 2012 Feb;13(2):172-80. doi: 10.1016/S1470-2045(11)70303-5. Epub 2011 Dec 15.
• Liu Z, Wang D, Li G, Yi M, Zhang Z, Zhong G, Xu L, Jiang R, Zheng Y, Huang L, Peng Y, Liang L, Li J, Liu Y, Lai J, Lv X, Xu Y, Liu Q, Wang Z, Liu Z, Yang Q, Nie L, Lei J, Huang X, Liu Z, Jiang W. Neoadjuvant with low-dose radiotherapy, tislelizumab, albumin-bound paclitaxel, and cisplatin for resectable locally advanced head and neck squamous cell carcinoma: phase II single-arm trial. Nat Commun. 2025 May 17;16(1):4608. doi: 10.1038/s41467-025-59865-1.
• Li S, Li K, Wang K, Yu H, Wang X, Shi M, Liang Z, Yang Z, Hu Y, Li Y, Liu W, Li H, Cheng S, Ye L, Yang Y. Low-dose radiotherapy combined with dual PD-L1 and VEGFA blockade elicits antitumor response in hepatocellular carcinoma mediated by activated intratumoral CD8+ exhausted-like T cells. Nat Commun. 2023 Nov 24;14(1):7709. doi: 10.1038/s41467-023-43462-1.
• Chen J, Levy A, Tian AL, Huang X, Cai G, Fidelle M, Rauber C, Ly P, Pizzato E, Sitterle L, Piccinno G, Liu P, Durand S, Mao M, Zhao L, Iebba V, Felchle H, Mallard de La Varende AL, Fischer JC, Thomas S, Greten TF, Jones JC, Monge C, Demaria S, Formenti S, Belluomini L, Dionisi V, Massard C, Blanchard P, Robert C, Quevrin C, Lopes E, Clemenson C, Mondini M, Meziani L, Zhan Y, Zeng C, Cai Q, Morel D, Sun R, Laurent PA, Mangoni M, Di Cataldo V, Arilli C, Trommer M, Wegen S, Neppl S, Riechelmann RP, Camandaroba MP, Neto ES, Fournier PE, Segata N, Holicek P, Galluzzi L, Buque A, Alves Costa Silva C, Derosa L, Kroemer G, Chen C, Zitvogel L, Deutsch E. Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients. Cancer Cell. 2025 Mar 10;43(3):361-379.e10. doi: 10.1016/j.ccell.2025.02.010.
• Herrera FG, Ronet C, Ochoa de Olza M, Barras D, Crespo I, Andreatta M, Corria-Osorio J, Spill A, Benedetti F, Genolet R, Orcurto A, Imbimbo M, Ghisoni E, Navarro Rodrigo B, Berthold DR, Sarivalasis A, Zaman K, Duran R, Dromain C, Prior J, Schaefer N, Bourhis J, Dimopoulou G, Tsourti Z, Messemaker M, Smith T, Warren SE, Foukas P, Rusakiewicz S, Pittet MJ, Zimmermann S, Sempoux C, Dafni U, Harari A, Kandalaft LE, Carmona SJ, Dangaj Laniti D, Irving M, Coukos G. Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy. Cancer Discov. 2022 Jan;12(1):108-133. doi: 10.1158/2159-8290.CD-21-0003. Epub 2021 Sep 3.
• Zhou L, Liu Y, Wu Y, Yang X, Spring Kong FM, Lu Y, Xue J. Low-dose radiation therapy mobilizes antitumor immunity: New findings and future perspectives. Int J Cancer. 2024 Apr 1;154(7):1143-1157. doi: 10.1002/ijc.34801. Epub 2023 Dec 7.
• Herrera FG, Romero P, Coukos G. Lighting up the tumor fire with low-dose irradiation. Trends Immunol. 2022 Mar;43(3):173-179. doi: 10.1016/j.it.2022.01.006. Epub 2022 Jan 31.
• Zhang Z, Liu X, Chen D, Yu J. Radiotherapy combined with immunotherapy: the dawn of cancer treatment. Signal Transduct Target Ther. 2022 Jul 29;7(1):258. doi: 10.1038/s41392-022-01102-y.
• Yang Y, Pan J, Wang H, Zhao Y, Qu S, Chen N, Chen X, Sun Y, He X, Hu C, Lin L, Yu Q, Wang S, Wang G, Lei F, Wen J, Yang K, Lin Z, Guo Y, Chen S, Huang X, Wu Y, Liang L, Chen C, Bai F, Ma X, Zhang Y, Leaw S, Zhang L, Fang W. Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309). Cancer Cell. 2023 Jun 12;41(6):1061-1072.e4. doi: 10.1016/j.ccell.2023.04.014. Epub 2023 May 18.
• Yang Y, Qu S, Li J, Hu C, Xu M, Li W, Zhou T, Shen L, Wu H, Lang J, Hu G, Luo Z, Fu Z, Qu S, Feng W, Chen X, Lin S, Zhang W, Li X, Sun Y, Lin Z, Lin Q, Lei F, Long J, Hong J, Huang X, Zeng L, Wang P, He X, Zhang B, Yang Q, Zhang X, Zou J, Fang W, Zhang L. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1162-1174. doi: 10.1016/S1470-2045(21)00302-8. Epub 2021 Jun 23.
• 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.
• Prawira A, Oosting SF, Chen TW, Delos Santos KA, Saluja R, Wang L, Siu LL, Chan KKW, Hansen AR. Systemic therapies for recurrent or metastatic nasopharyngeal carcinoma: a systematic review. Br J Cancer. 2017 Dec 5;117(12):1743-1752. doi: 10.1038/bjc.2017.357. Epub 2017 Oct 24.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2026
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): January 30, 2030

Study Registration Dates

• First Submitted: December 24, 2025
• First Submitted That Met QC Criteria: December 24, 2025
• First Posted (Actual): January 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PD-1 antibody; Recurrent/Metastatic Nasopharyngeal Carcinoma; Low dose radiotherapy
• 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 Neoplasms; Nasopharyngeal Carcinoma; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Platinum Compounds; Gemcitabine; Cisplatin; toripalimab
• Other Study ID Numbers: 2025-FXY-451-FLK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No