Evaluating a new treatment for relapsed or refractory NK/T-cell lymphoma

A Phase Ib/II Clinical Study Evaluating the Safety and Efficacy of Tislelizumab in Combination With Golidocitinib and Selinexor for the Treatment of Relapsed/Refractory Natural Killer/T-Cell Lymphoma (NKTCL)

This study is testing a new combination treatment for people with relapsed or hard-to-treat NK/T-cell lymphoma to see if it can help them when other treatments haven't worked.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 68 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, tislezumab, golidocitinib, tislelizumab
• Locations: 1 site (Shanghai, Shangai)
• Trial ID: NCT06966154 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter Phase Ib/II clinical trial investigates the safety, tolerability, and preliminary efficacy of a combination therapy involving tislelizumab, golidocitinib, and selinexor for patients with relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL). The study aims to address the unmet need for effective treatments in this aggressive lymphoma subtype, particularly for patients who have not responded to previous therapies. The trial will assess dose escalation to establish the recommended Phase II dose while monitoring for dose-limiting toxicities. The combination targets multiple pathways involved in the disease's pathogenesis, potentially improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates include patients with histopathologically confirmed extranodal NK/T-cell lymphoma who have relapsed or are refractory after prior asparaginase-based chemotherapy.

Not a fit: Patients who have not received prior anti-PD-1 therapy or those with other types of lymphoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with relapsed or refractory NK/T-cell lymphoma.

How similar studies have performed: While there have been studies exploring similar combination therapies, this specific approach targeting R/R ENKTL is novel and has not been extensively tested.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shangai

• Dept of lymphoma and medical oncology, Shanghai Cancer Center — Shanghai, Shangai, China (Recruiting)

Study contacts

• Study coordinator: Rong Tao, MD & PhD

Conditions Natural Killer/T-cell Lymphoma; Relapsed or Refractory Lymphoma Including ENKL; natural killer/T-cell lymphoma; Immune checkpointor inhibitor; tislelizumab; golidocitinib; selinexor