A Phase Ib/II Clinical Study Evaluating the Safety and Efficacy of Tislelizumab in Combination With Golidocitinib and Selinexor for the Treatment of R/R NKTCL

Inclusion Criteria:

* Voluntarily participate in the clinical study; fully understand and provide informed consent (via a signed Informed Consent Form, ICF); willing and able to comply with all trial procedures.
* Histopathologically confirmed diagnosis of extranodal NK/T-cell lymphoma, nasal type (NKTCL) by the participating study center.
* Relapsed or refractory NKTCL after failure of asparaginase-based chemotherapy ± radiotherapy:

  * Relapse: Disease recurrence \>6 months after achieving complete response (CR) to prior therapy.
  * Refractory: Failure to achieve CR or disease progression after adequate systemic therapy (≥4 cycles of a combination regimen).
  * For Phase II: Patients must have received prior anti-PD-1 monoclonal antibody therapy and remain refractory.
* At least one measurable or evaluable lesion per Lugano 2014 criteria:

  * Measurable lesion: CT/MRI: Longest diameter ≥1.5 cm (lymph nodes) or ≥1.0 cm (extranodal lesions).Post-radiation lesions require radiological evidence of progression.
  * Evaluable lesion: FDG-PET: Lymph node/extranodal lesion with uptake \> liver and imaging consistent with lymphoma.
* Age ≥18 years at the time of ICF signing.
* Life expectancy \>12 weeks.
* ECOG performance status 0-2.
* Adequate organ and bone marrow function:

  * Hematology (no transfusion/G-CSF support within 14 days): ANC ≥1.5×10⁹/L (≥0.5×10⁹/L if bone marrow involvement)；Platelets ≥100×10⁹/L (≥50×10⁹/L if bone marrow involvement)；Hemoglobin ≥8.0 g/dL.
  * Liver function: Total bilirubin ≤1.5×ULN (≤3.0×ULN for Gilbert's syndrome or liver involvement).

ALT/AST ≤2.5×ULN (≤5.0×ULN with liver involvement).

* Renal function: Serum creatinine ≤1.5×ULN OR creatinine clearance (Cockcroft-Gault) ≥50 mL/min.
* Coagulation: INR ≤1.5×ULN; PT/APTT ≤1.5×ULN (unless on anticoagulants within therapeutic range).
* Cardiac function: LVEF ≥50% by echocardiography (ECHO).

  * Recovery from prior anticancer therapy toxicities to CTCAE v5.0 Grade ≤1 or baseline. Exceptions: Irreversible Grade 2 toxicities unlikely to worsen during the study (e.g., neuropathy, alopecia) per investigator's assessment.
  * For women of childbearing potential (WOCBP): Negative serum pregnancy test within 7 days before enrollment. WOCBP and male participants with WOCBP partners must agree to use effective contraception from ICF signing until ≥6 months after the last study dose.

Exclusion Criteria:

* History of malignancy within the past 5 years, with the exception of: Locally curable malignancies treated with curative intent (e.g., basal or squamous cell skin cancer, thyroid carcinoma, superficial bladder cancer, or in situ carcinoma of the prostate, cervix, or breast).
* Any of the following prior treatments:

  * History of allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 5 years prior to the first dose (patients with allo-HSCT \>5 years before the first dose and no active graft-versus-host disease may enroll).
  * Autologous hematopoietic stem cell transplantation (auto-HSCT) within 3 months prior to the first dose.
  * Prior use of JAK inhibitors, STAT3 inhibitors, or XPO1 inhibitors.
  * Current use of vitamin K antagonists, antiplatelet agents, or anticoagulants (or inability to discontinue within 1 week before the first dose).
  * Systemic glucocorticoids or immunosuppressants within 14 days prior to enrollment (allowed: topical, ocular, intra-articular, intranasal, or inhaled glucocorticoids; short-term \[≤7 days\] prophylactic use for non-autoimmune conditions).
  * Cytotoxic chemotherapy within 14 days prior to enrollment.
  * Systemic anticancer therapy (including monoclonal antibodies or immunotherapy) within 4 weeks prior to the first dose.
  * Major organ surgery within 6 weeks or radiotherapy within 90 days prior to enrollment.
  * Radioimmunoconjugate therapy within 10 weeks prior to enrollment.
  * Use of other investigational drugs requiring investigator's risk-benefit assessment.
  * Participation in other clinical trials with investigational drugs within 30 days prior to enrollment.
  * Vaccines (except influenza vaccines) within 28 days prior to enrollment.
* Active infections, including:

  * Active or latent tuberculosis (positive tuberculin skin test \[PPD\] with induration ≥10 mm or radiologically confirmed active lesions).
  * Known HIV infection or AIDS.
  * Chronic active hepatitis B or C:

HBV: Exclude if HBV DNA detectable (↑center-specific ULN). HCV: Exclude if HCV RNA detectable (↑center-specific ULN).

* Other active viral infections (e.g., herpes zoster, CMV) requiring treatment. Infections requiring intravenous antimicrobial therapy.

  * Uncontrolled cardiac conditions, including:
* NYHA Class \>II heart failure.
* Unstable angina.
* Myocardial infarction within 1 year.
* Clinically significant arrhythmias requiring intervention.

  * Persistent drug-related toxicities \>CTCAE Grade 1 (excluding alopecia) at baseline.
  * Uncontrolled nausea/vomiting, chronic gastrointestinal diseases, dysphagia, or prior bowel resection affecting drug absorption.
  * Pregnancy, lactation, or refusal to use contraception by participants of reproductive potential.
  * Psychiatric disorders or inability to provide informed consent.
  * Other conditions deemed unsuitable for study participation by the investigator.