Low-dose radiotherapy with toripalimab and chemotherapy for recurrent or metastatic nasopharyngeal cancer

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

This will test whether adding low-dose radiotherapy to toripalimab plus gemcitabine‑cisplatin helps people with recurrent or metastatic nasopharyngeal cancer respond better while staying safe.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, toripalimab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07325539 on ClinicalTrials.gov

What this trial studies

This is a prospective, open-label, single-arm Phase II trial at Sun Yat-sen University Cancer Center testing the combination of low-dose radiotherapy (LDRT), toripalimab, and gemcitabine‑cisplatin (GP) chemotherapy. Enrolled patients receive a planned regimen of LDRT together with the PD-1 antibody toripalimab and standard doses of gemcitabine and cisplatin. The trial will measure tumor response by RECIST v1.1, record adverse events, and follow progression-free and overall survival outcomes. Eligible participants are adults 18–65 with histologically confirmed non-keratinizing nasopharyngeal carcinoma, ECOG 0–1, measurable disease, adequate organ function, and no prior systemic therapy for recurrent or metastatic lesions.

Who should consider this trial

Good fit: Adults aged 18–65 with non-keratinizing (WHO type II/III) recurrent or newly metastatic nasopharyngeal carcinoma, ECOG 0–1, measurable disease, adequate organ function, and no prior systemic therapy for recurrent/metastatic lesions are the intended participants.

Not a fit: Patients outside the 18–65 age range, with keratinizing histology, poor performance status, significant organ dysfunction, prior systemic therapy for recurrent/metastatic disease, or inability to travel to the study center are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, the combination could increase tumor response rates and extend the time patients live without disease progression.

How similar studies have performed: PD-1 inhibitors combined with chemotherapy have shown benefit in metastatic NPC, but combining those agents with low-dose radiotherapy is a newer approach with limited prior clinical data.

Eligibility criteria

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.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Jun Ma, M.D. — Sun Yat-sen University
• Study coordinator: Jun Ma, M.D.

Conditions Nasopharyngeal Cancinoma; Nasopharangeal Cancer; PD-1 antibody; Low dose radiotherapy; Recurrent/Metastatic Nasopharyngeal Carcinoma