PD-1 antibody therapy combined with radiotherapy for early extranodal NK/T‑cell lymphoma

A Prospective Study to Evaluate the Efficacy and Safety of PD-1 Monoclonal Antibody-based Stratified Targeted Therapy Combined With Concurrent Radiotherapy for Patients With Treatment-naive Early-stage Nasal-type NK/T-cell Lymphoma

This trial will try PD‑1 antibody treatment with concurrent radiotherapy, sometimes adding targeted drugs like chidamide or golidocitinib, to see if it helps adults with previously untreated early-stage nasal-type NK/T-cell lymphoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: gorlitinib, methotrexate, cyclophosphamide
• Locations: 1 site (Shanghai)
• Trial ID: NCT07380984 on ClinicalTrials.gov

What this trial studies

This Phase 2, response-adapted protocol enrolls adults with newly diagnosed stage I–II extranodal NK/T‑cell lymphoma (nasal type) and delivers PD‑1 monoclonal antibody therapy together with concurrent radiotherapy. Patients receive stratified targeted agents (for example, chidamide or golidocitinib) based on predefined response/adaptive rules to personalize therapy intensity. The approach is designed to integrate systemic immunotherapy with local control by radiotherapy while aiming to limit exposure to more toxic combinations. Key objectives include improving overall treatment outcomes and reducing treatment-related toxicity compared with historical regimens.

Who should consider this trial

Good fit: Adults aged 18 or older with newly diagnosed, untreated extranodal NK/T-cell lymphoma (nasal type), Ann Arbor stage I–II, measurable disease, ECOG 0–2, and adequate bone marrow, liver, and kidney function are eligible.

Not a fit: Patients with advanced stage (III–IV) disease, prior anti-lymphoma therapy, severely impaired organ function, or ECOG performance status >2 are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase cure rates and reduce treatment-related toxicity for patients with early-stage nasal-type NK/T-cell lymphoma.

How similar studies have performed: PD‑1 inhibitors have shown meaningful activity in relapsed/refractory NK/T‑cell lymphoma, but using PD‑1 therapy up front with concurrent radiotherapy in previously untreated early-stage disease is a newer and less-tested strategy.

Eligibility criteria

Inclusion Criteria:

* The subject has histopathologically confirmed extranodal NK/T-cell lymphoma, nasal type (according to the 2022 WHO classification).
* No prior history of anti-lymphoma therapy.
* Age ≥ 18 years.
* Life expectancy \> 3 months.
* Ann Arbor stage I-II.
* At least one measurable/evaluable disease site confirmed by diagnostic biopsy prior to the initiation of treatment.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
* Signed informed consent form (ICF).
* Willingness and ability to comply with the study protocol.
* Sufficient bone marrow, hepatic, and renal function, defined as:

  1. Absolute neutrophil count (ANC) \> 1,000/μL
  2. Platelet count \> 50,000/μL
  3. Hemoglobin \> 9 g/dL
  4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3× upper limit of normal (ULN)
  5. Serum total bilirubin \< 1.5 × ULN (patients with Gilbert's syndrome are eligible)
  6. Serum creatinine \< 2 × ULN or creatinine clearance \> 50 mL/min
* Availability of tumor tissue samples (preferably fresh tissue; archived tissue samples are acceptable).
* For women of childbearing potential, agreement to use adequate contraception to avoid pregnancy during the study treatment period.
* For male, agreement to remain abstinent or use a barrier method of contraception.

Exclusion Criteria:

* Advanced-stage disease (Ann Arbor Stage III-IV).
* Nonnasal-type NKTCL.
* A history of autoimmune disease requiring systemic treatment (i.e., with disease-modifying antirheumatic drugs, corticosteroids, or immunosuppressants) within the past 2 years, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody-associated vasculopathy, granulomatosis with polyangiitis (Wegener's), Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.

The following conditions are permissible for enrollment: patients with autoimmune hypothyroidism or type 1 diabetes receiving stable treatment; hormone replacement therapy (e.g., levothyroxine, insulin, or supplementation with physiological hormones for adrenal or pituitary insufficiency) is not considered systemic therapy and is allowed.

* A history of other invasive malignancies within the past 3 years that has not been treated with curative intent or is currently receiving anticancer therapy (including hormonal therapy for breast or prostate cancer).
* A history of (non-infectious) pneumonia requiring corticosteroid therapy; or clinical evidence of interstitial lung disease or active, non-infectious pneumonia.
* Active infections requiring systemic treatment, including:

  1. A known history of active tuberculosis;
  2. Positive results for HBsAg, HCV, or HIV; HBV seropositivity is permitted only if HBV DNA \< 1000 IU/mL;
  3. Active viral infections other than hepatitis B and C (e.g., herpes zoster).
* Severe cardiovascular disease, including myocardial infarction, unstable arrhythmia, or unstable angina occurring within the past 3 months.
* Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.
* Administration of live-attenuated vaccines within 4 weeks prior to the initiation of study treatment; patients are prohibited from receiving live-attenuated vaccines during the study period, including influenza vaccines.
* Use of systemic immunosuppressive agents within 2 weeks prior to the initiation of study treatment, or planned use of such agents during the study period, including cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) drugs.
* Evidence of central nervous system involvement.
* A history of allogeneic tissue/solid organ transplantation.
* A history of severe hypersensitivity reactions (Grade ≥ 3) to PD-1 monoclonal antibodies and/or their excipients, or to gorlitinib and/or its excipients.
* Any other factors judged by the investigator to potentially affect compliance with the study protocol.

Where this trial is running

Shanghai

• Ruijin Hospital, Shanghai JiaoTong University School of Medicine — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Weili Zhao

Conditions Natural Killer/T-cell Lymphoma