Radscopal Radiotherapy Plus Immunotherapy for Chemotherapy-Ineligible Patients With Newly Diagnosed Metastatic Nasopharyngeal Cancer: A Single-Center, Open-Label, Phase II Study

NCT07756190 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: SL-B2026-384-02
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The RADIANCE trial plans to enroll patients with chemotherapy-ineligible de novo metastatic nasopharyngeal carcinoma (AJCC 9th edition, TxNxM1). Participants will receive Radscopal radiotherapy, consisting of low-dose radiotherapy to the primary lesions and stereotactic body radiotherapy to distant metastatic lesions, in combination with sintilimab and ipilimumab. The study will evaluate the objective response rate of the primary lesions, systemic disease control as measured by progression-free survival and overall survival, and the safety and tolerability of this treatment regimen. The main questions this study aims to answer are: Does this treatment improve efficacy with acceptable safety in chemotherapy-ineligible patients? Does Radscopal radiotherapy enhance systemic antitumor immunity, and what is the Radscopal Response Rate? What clinical and immunological factors are associated with the Radscopal effect, and what mechanisms may underlie this effect?

Conditions

Nasopharyngeal Carcinoma (NPC); Metastatic Nasopharyngeal Carcinoma

Keywords

Metastatic Nasopharyngeal Carcinoma; Immunotherapy; Radiotherapy; Combined Modality Therapy; Tumor Immunity

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) of Primary Lesions

  The proportion of participants with confirmed complete response or partial response in measurable primary lesions (nasopharyngeal and neck), assessed according to RECIST version 1.1.

  6 months

Secondary Outcomes (8)

• Objective Response Rate by Lesion Irradiation Type

  6 months

• Disease Control Rate (DCR)

  6 months

• Duration of Response (DoR)

  1 year

• One-Year Progression-Free Survival (PFS)

  1 year

• One-Year Overall Survival (OS)

  1 year

Other Outcomes (3)

• Objective Response Rate (ORR) by Prespecified Subgroups

  6 months

• Immune cell subsets of tissue samples

  From baseline to tumor response assessment

• Serum cytokine levels

  From baseline to the end of treatment

Study Arms (1)

Radscopal Radiotherapy Plus Sintilimab and Ipilimumab

EXPERIMENTAL

Participants will receive LDRT to the primary lesions, SBRT to selected metastatic lesions, and intravenous sintilimab and ipilimumab.

Drug: Sintilimab; Drug: ipilimumab; Radiation: Radscopal Radiotherapy

Interventions

Sintilimab DRUG

Sintilimab 200 mg will be administered by intravenous infusion once every 2 weeks, starting within 7 days after completion of stereotactic body radiotherapy, until unacceptable toxicity, disease progression, or for up to 6 months.

Also known as: PD-1 antibody, IBI308

Radscopal Radiotherapy Plus Sintilimab and Ipilimumab

ipilimumab DRUG

Ipilimumab 1 mg/kg will be administered by intravenous infusion once every 6 weeks for 2 cycles, beginning on the same day as the first sintilimab infusion.

Also known as: CTLA-4 antibody, IBI310

Radscopal Radiotherapy Plus Sintilimab and Ipilimumab

Radscopal Radiotherapy RADIATION

Participants will receive low-dose radiotherapy to the primary tumors at 8 Gy in 8 fractions. Stereotactic body radiotherapy will also be delivered to distant metastatic lesions at 24 Gy in 3 fractions.

Also known as: LDRT combined with SBRT

Radscopal Radiotherapy Plus Sintilimab and Ipilimumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age 18-80 years.
• \. Histologically or cytologically confirmed de novo metastatic nasopharyngeal carcinoma (TxNxM1 according to AJCC 9th edition), with ≤10 measurable metastatic lesions.
• \. At least one measurable nasopharyngeal lesion suitable for low-dose radiotherapy and at least one distant metastatic lesion suitable for stereotactic body radiotherapy.
• \. ECOG performance status 0-2.
• \. PD-L1 combined positive score (CPS) ≥1.
• \. Chemotherapy-ineligible, including patients medically unsuitable for platinum-based chemotherapy or patients who refuse standard platinum-based chemotherapy after being fully informed.
• \. Life expectancy ≥6 months.
• \. Adequate organ function, including ANC ≥1.0 × 10\^9/L, platelets ≥75 × 10\^9/L, hemoglobin ≥80 g/L, ALT/AST ≤3 × ULN, bilirubin ≤2 × ULN, creatinine clearance ≥30 mL/min, and LVEF ≥45% or normal echocardiography.
• \. No major surgery within 1 month before enrollment.
• \. No immunosuppressive or immunomodulatory therapy within 1 month before immune checkpoint inhibitor treatment.
• \. Written informed consent and ability to comply with study procedures and follow-up.

You may not qualify if:

• \. Age \<18 years.
• \. \>10 metastatic lesions, meningeal metastasis, spinal cord compression, or lesions unsuitable for safe stereotactic body radiotherapy.
• \. Other malignancy within 5 years, except cured basal cell carcinoma, squamous cell carcinoma of the skin, papillary thyroid carcinoma, or cervical carcinoma in situ.
• \. Prior systemic immune checkpoint inhibitor therapy or prior nasopharyngeal radiotherapy.
• \. Active hepatitis B infection, defined as HBsAg positivity with HBV DNA \>200 IU/mL or \>1000 copies/mL.
• \. Positive hepatitis C virus antibody.
• \. Active, known, or suspected autoimmune disease, except type 1 diabetes, hypothyroidism requiring only hormone replacement, or skin disorders not requiring systemic treatment.
• \. Systemic corticosteroids equivalent to \>10 mg prednisone daily or other immunosuppressive therapy within 28 days before informed consent, except low-dose, inhaled, or topical corticosteroids.
• \. Active tuberculosis, active tuberculosis within the previous year, or prior active tuberculosis without documented adequate anti-tuberculosis treatment.
• \. History of interstitial lung disease.
• \. Uncontrolled diabetes mellitus (fasting blood glucose \>13.9 mmol/L).
• \. Live vaccine within 30 days before informed consent or planned live vaccination.
• \. Known allergy to macromolecular protein preparations or to any component of sintilimab or ipilimumab.
• \. HIV infection.
• \. Any condition that may affect participant safety or compliance, including uncontrolled cardiovascular disease, active infection requiring systemic treatment, psychiatric illness, severe cognitive impairment, suicidal tendency, or relevant psychological, family, or social factors.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (6)

• Huang J, Theelen WSME, Belcaid Z, Najjar M, van der Geest D, Singh D, Cherry C, Balan A, White JR, Wehr J, Karchin R, Niknafs N, van den Heuvel MM, Velculescu VE, Smith KN, Baas P, Anagnostou V. Combination of pembrolizumab and radiotherapy induces systemic antitumor immune responses in immunologically cold non-small cell lung cancer. Nat Cancer. 2025 Oct;6(10):1676-1692. doi: 10.1038/s43018-025-01018-w. Epub 2025 Jul 22.

  PMID: 40696153 BACKGROUND

• Zhou X, Zhou L, Yao Z, Huang M, Gong Y, Zou B, Zhu J, Liu Y, Peng F, Zhang Y, Yu M, Li Y, Na F, Wu Y, Kang K, Xiu W, Zhang X, Zhou L, Xu Y, Wang J, Wang Y, Yang X, Wu Y, Li R, Zhang Y, Yang Z, Zhou Z, Bai J, Yi X, Tong R, Yin L, Chen C, Niedermann G, Lu Y, Xue J. Safety and Tolerability of Low-Dose Radiation and Stereotactic Body Radiotherapy + Sintilimab for Treatment-Naive Stage IV PD-L1+ Non-Small Cell Lung Cancer Patients. Clin Cancer Res. 2023 Oct 13;29(20):4098-4108. doi: 10.1158/1078-0432.CCR-23-0315.

  PMID: 37581611 BACKGROUND

• 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.

  PMID: 35906199 BACKGROUND

• Ngwa W, Irabor OC, Schoenfeld JD, Hesser J, Demaria S, Formenti SC. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer. 2018 May;18(5):313-322. doi: 10.1038/nrc.2018.6. Epub 2018 Feb 16.

  PMID: 29449659 BACKGROUND

• Darragh LB, Knitz MM, Hu J, Clambey ET, Backus J, Dumit A, Samedi V, Bubak A, Greene C, Waxweiler T, Mehrotra S, Bhatia S, Gadwa J, Bickett T, Piper M, Fakhoury K, Liu A, Petit J, Bowles D, Thaker A, Atiyeh K, Goddard J, Hoyer R, Van Bokhoven A, Jordan K, Jimeno A, D'Alessandro A, Raben D, McDermott JD, Karam SD. A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC. Nat Cancer. 2022 Nov;3(11):1300-1317. doi: 10.1038/s43018-022-00450-6. Epub 2022 Nov 25.

  PMID: 36434392 BACKGROUND

• Lim DW, Kao HF, Suteja L, Li CH, Quah HS, Tan DS, Tan SH, Tan EH, Tan WL, Lee JN, Wee FY, Jain A, Goh BC, Chua MLK, Liao BC, Ng QS, Hong RL, Ang MK, Yeong JP, Iyer NG. Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma. Nat Commun. 2023 May 15;14(1):2781. doi: 10.1038/s41467-023-38407-7.

  PMID: 37188668 BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

sintilimab; spartalizumab; Ipilimumab; Radiosurgery

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Yanping Mao, MD, PhD

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanping Mao, MD, PhD

CONTACT

+86 02087343545; maoyp@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Principal Investigator

Study Record Dates

• First Submitted: July 31, 2026
• First Posted: August 10, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 30, 2029
• Study Completion (Estimated): June 30, 2030
• Last Updated: August 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: For 2 years starting 12 months after publication of the primary trial report.
• Access Criteria: Authoritative researchers who provide a methodologically sound proposal for individual participant data meta-analysis.

Locations

CN (1)