PD-1 Antibody-based Therapy With Concurrent RT for Early-stage NKTCL

Official title

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

Overview

Natural killer/T-cell lymphoma (nasal type) is a mature T/NK-cell lymphoma closely associated with Epstein-Barr virus (EBV), with a high prevalence among populations in Asia and South America. It primarily occurs at extranodal sites, including the nasal/paranasal regions, skin, gastrointestinal tract, and other organs. This study focuses on previously untreated patients with early-stage NKTCL (nasal type), exploring a response-adapted comprehensive therapeutic strategy that combines PD-1 monoclonal antibody-based stratified targeted therapy with concurrent radiotherapy. The aim is to provide integrated management for early-stage extranodal NK/T-cell lymphoma (nasal type), and reduce toxicity while improving overall treatment outcomes for patients.

Interventions

• Drug PD-1 antibody
  Administration of PD-1 mAb will start on Day 1 of radiotherapy (C1D1) at a dose of 200 mg via intravenous infusion over 30 minutes or longer, once every 3 weeks, cycle 1 - cycle 6
• Radiation radiotherapy
  Concurrent standard involved-site radiotherapy (ISRT)
• Drug Chidamide
  The dosage of chidamide will follow a dose-escalation design: 20 mg twice weekly (biw) in the first stage, then escalated to 30 mg biw, using the Bayesian Optimal Interval (BOIN) design to determine the recommended dose, followed by dose expansion in the second stage, every 3 weeks, cycle 4 - cycle 6.
• Drug golidocitinib
  Golidocitinib will be administered at a dose of 150 mg once daily (qd), every 3 weeks, cycle 4 - cycle 6.

Primary outcome measures

• 2-year progression-free survival rate [Time frame: Baseline up to data cut-off (up to 24 months).]

Secondary outcome measures (7)

• Complete Response Rate [Time frame: At the end of cycle 3, cycle 6 after treatment start.]
• Overall Response Rate [Time frame: At the end of cycle 3, cycle 6 after treatment start.]
• 2-year overall survival rate [Time frame: Baseline up to data cut-off (up to 24 months).]
• 2-year event-free survival rate [Time frame: Baseline up to data cut-off (up to 24 months).]
• Duration of Response [Time frame: From enrollment to study completion (up to approximately 24 months).]
• Treatment-Related Adverse Events rate [Time frame: From enrollment to study completion (up to approximately 24 months).]
• The change of plasma EB virus DNA load [Time frame: Baseline up to data cut-off (up to 24 months).]

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:

• Absolute neutrophil count (ANC) > 1,000/μL
• Platelet count > 50,000/μL
• Hemoglobin > 9 g/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3× upper limit of normal (ULN)
• Serum total bilirubin < 1.5 × ULN (patients with Gilbert's syndrome are eligible)
• 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:

• A known history of active tuberculosis;
• Positive results for HBsAg, HCV, or HIV; HBV seropositivity is permitted only if HBV DNA < 1000 IU/mL;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Ruijin Hospital, Shanghai JiaoTong University School of Medicine — Shanghai

Identifiers

NCT: NCT07380984 · NOVEL-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗