High-low dose radiation plus anti-PD-1 followed by full-course radiation for recurrent nasopharyngeal cancer

Induction Therapy With High-Low Dose Radiotherapy Combined With Anti-PD-1 Monoclonal Antibody Followed by Definitive Radiotherapy in Recurrent Nasopharyngeal Carcinoma: A Single-Arm, Single-Center Phase II Trial

This approach tests whether a short induction of mixed low- and high-dose radiation with an anti-PD-1 drug, followed by full-course radiation and immunotherapy maintenance, can shrink recurrent nasopharyngeal cancer in patients who cannot have surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 23 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Jiangxi Provincial Cancer Hospital (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Nanchang, Jiangxi)
• Trial ID: NCT07277764 on ClinicalTrials.gov

What this trial studies

This single-arm, single-center Phase II protocol delivers three fractions of low-dose radiotherapy plus three high-dose boosts to the tumor core together with anti-PD-1 (240 mg IV on Day 1 and Day 22) as induction. After a 21–28 day interval participants receive definitive IMRT (2 Gy ×28 fractions) without concurrent immunotherapy, then begin anti-PD-1 maintenance (240 mg IV every 3 weeks) for up to 12 months or until progression or unacceptable toxicity. The primary endpoint is objective response rate at 3 months after radiotherapy; secondary endpoints include 3-year overall survival, 3-year progression-free survival, safety per CTCAE v5.0, and quality of life by EORTC QLQ-C30. Key inclusion criteria are histologically confirmed non-keratinizing NPC (WHO II/III), local recurrence ≥1 year after prior therapy, rT2–rT4 disease, ECOG 0–1, adequate organ function, and no distant metastases or prior PD-1/PD-L1 therapy.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed non-keratinizing recurrent NPC (rT2–rT4), no distant metastasis, ECOG 0–1, adequate organ function, and who are ineligible for salvage surgery.

Not a fit: Patients with distant metastases, prior PD-1/PD-L1 therapy, active autoimmune disease, uncontrolled comorbidities, or active infections are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase tumor shrinkage and local control for patients with recurrent nasopharyngeal cancer who are not candidates for salvage surgery.

How similar studies have performed: PD-1 inhibitors have shown activity in recurrent/metastatic NPC and combining immunotherapy with radiation has biological rationale, but this specific induction high-low radiation followed by definitive radiotherapy is relatively novel and not yet widely proven.

Eligibility criteria

Inclusion Criteria：

Histologically confirmed non-keratinizing NPC (WHO II/III); local (± regional) recurrence ≥1 year after prior radical therapy; surgery-ineligible;

rT2-rT4 (AJCC 8th); ECOG 0-1;

Adequate organ function (hematologic, hepatic, renal, coagulation per protocol thresholds);

Contraception requirements per protocol; signed informed consent.

Exclusion Criteria：

Distant metastasis at recurrence; active necrosis at recurrence; active/previous autoimmune disease; prior PD-1/PD-L1 therapy; uncontrolled comorbidities; active infections (HBV/HCV/HIV criteria per protocol); interstitial lung disease/pneumonitis; pregnancy/lactation; other protocol-specified exclusions.

Where this trial is running

Nanchang, Jiangxi

• Jiangxi Cancer Hospital — Nanchang, Jiangxi, China (Recruiting)

Study contacts

• Study coordinator: Jingao Li Prof. Jingao Li, MD

Conditions Nasopharyngeal Carcinoma; Recurrent Nasopharyngeal Neoplasms; recurrent NPC; re-irradiation; high-low dose radiotherapy; induction radio-immunotherapy; PD-1 inhibitor