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

NCT06966154 | Recruiting Phase 1 DMC

• 1 other identifier: SHCA-NKT-202501
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label, multicenter Ib/II phase clinical trial investigates the safety, tolerability, and preliminary efficacy of tislezumab (anti-PD-1 monoclonal antibody), golidocitinib (JAK1/STAT3 signaling pathway inhibitor), and selinexor (selective inhibitor of nuclear export, XPO1 antagonist) in patients with relapsed/refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL) progressing after ≥1 line of L-asparaginase-containing chemotherapy or chemoradiotherapy.

Conditions

Natural Killer/T-cell Lymphoma; Relapsed or Refractory Lymphoma Including ENKL

Keywords

natural killer/T-cell lymphoma; Immune checkpointor inhibitor; tislelizumab; golidocitinib; selinexor

Outcome Measures

Primary Outcomes (3)

• RP2D of golidocitinib in combination with selinexor

  Recommended Phase II Dose of golidocitinib in combination with selinexor

  4 weeks after the initiation of combination treatment

• Satety profile

  Safety profile, including: Incidence, severity, and drug-relatedness of adverse events (AEs) and serious adverse events (SAEs) per NCI CTCAE ver 5.0

  6 months after the last lose of combination treatment

• Overall response rate

  Phase II (Dose-Expansion Phase) part 12-week objective response rate (ORR) assessed per Lugano 2014 criteria for lymphoma response evaluation.

  12-weeks after the initiation of combination treatment

Secondary Outcomes (5)

• Complete Response Rate

  12-weeks after the initiation of combination treatment

• Duration of Response

  12 months after the last patient enrolled

• Progression-Free Survival (PFS)

  12 months after the last patient enrolled

• Overall survival(OS)

  12 months after the last patient enrolled

• Treatment-Emergent Adverse Events（TEAE）

  6 months after the last patient quit the trial treatment

Other Outcomes (1)

• Biomarkers

  6 months after the last patient enrolled

Study Arms (1)

tislezumab plus golidocitinib and selinexor

EXPERIMENTAL

Patients will receive Tislelizumab: Fixed intravenous dose of 200 mg every 3 weeks (Q3W). Golidocitinib: Dose-escalating oral regimens: Dose level A: 150 mg every other day (QOD). Dose level B: 150 mg once daily (QD). Selinexor: Dose-escalating oral regimens: Dose A: 40 mg once weekly (QW) . Dose B: 60 mg QW for 2 consecutive weeks, followed by 1 week off. Safety monitoring will be performed throughout each 3-week cycle, with dose escalation contingent on safety/tolerability assessments.

Drug: tislezumab; Drug: golidocitinib; Drug: Selinexor

Interventions

tislezumab DRUG

Tislelizumab will be administered intravenously at a fixed dose of 200 mg every 3 weeks (Q3W).

tislezumab plus golidocitinib and selinexor

golidocitinib DRUG

Golidocitinib: Dose-escalating oral regimens: Dose level A: 150 mg every other day (QOD). Dose level B: 150 mg once daily (QD).

tislezumab plus golidocitinib and selinexor

Selinexor DRUG

Selinexor: Dose-escalating oral regimens: Dose A: 40 mg once weekly (QW) . Dose B: 60 mg QW for 2 consecutive weeks, followed by 1 week off.

tislezumab plus golidocitinib and selinexor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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:

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Dept of lymphoma and medical oncology, Shanghai Cancer Center

Shanghai, Shangai, 200032, China

RECRUITING

Related Publications (5)

• Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, Khong PL, Loong F, Au-Yeung R, Iqbal J, Phipps C, Tse E. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017 Apr 27;129(17):2437-2442. doi: 10.1182/blood-2016-12-756841. Epub 2017 Feb 10.

  PMID: 28188133 BACKGROUND

• Tao R, Liu C, Zhang W, Zhu Y, Ma Y, Hao S. Selinexor With Anti-PD-1 Antibody as a Potentially Effective Regimen for Patients With Natural Killer/T-Cell Lymphoma Failing Prior L-Asparaginase and PD-1 Blockade. Oncologist. 2024 Jan 5;29(1):e90-e96. doi: 10.1093/oncolo/oyad241.

  PMID: 37616529 BACKGROUND

• Mathew D, Marmarelis ME, Foley C, Bauml JM, Ye D, Ghinnagow R, Ngiow SF, Klapholz M, Jun S, Zhang Z, Zorc R, Davis CW, Diehn M, Giles JR, Huang AC, Hwang WT, Zhang NR, Schoenfeld AJ, Carpenter EL, Langer CJ, Wherry EJ, Minn AJ. Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients. Science. 2024 Jun 21;384(6702):eadf1329. doi: 10.1126/science.adf1329. Epub 2024 Jun 21.

  PMID: 38900877 BACKGROUND

• Song Y, Malpica L, Cai Q, Zhao W, Zhou K, Wu J, Zhang H, Mehta-Shah N, Ding K, Liu Y, Li Z, Zhang L, Zheng M, Jin J, Yang H, Shuang Y, Yoon DH, Gao S, Li W, Zhai Z, Zou L, Xi Y, Koh Y, Li F, Prince M, Zhou H, Lin L, Liu H, Allen P, Roncolato F, Yang Z, Kim WS, Zhu J. Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study. Lancet Oncol. 2024 Jan;25(1):117-125. doi: 10.1016/S1470-2045(23)00589-2. Epub 2023 Dec 9.

  PMID: 38092009 BACKGROUND

• Tao R, Fan L, Song Y, Hu Y, Zhang W, Wang Y, Xu W, Li J. Sintilimab for relapsed/refractory extranodal NK/T cell lymphoma: a multicenter, single-arm, phase 2 trial (ORIENT-4). Signal Transduct Target Ther. 2021 Oct 27;6(1):365. doi: 10.1038/s41392-021-00768-0.

  PMID: 34702811 BACKGROUND

MeSH Terms

Conditions

Recurrence

Interventions

selinexor

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Rong Tao, MD & PhD

CONTACT

008621-64175590; hkutao@hotmail.com

Chuanxu Liu, MD

CONTACT

008621-64175590; liuchaunxu@shca.or.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor & Chief

Model Details: Phase Ib (Safety Run-In Section) Guided by the Bayesian Optimal Interval (BOIN) design, the study explores the combined dosing of golidocitinib, selinexor, and tislelizumab across 2 dose levels and 4 dosing cohorts . Patients are sequentially enrolled in chronological order and assigned to one of the following combination regimens: Golidocitinib: 2 dose groups. Selinexor: 2 dose groups.Randomization is implemented within each dose level. The first treatment cycle (28-day cycle) is designated as the dose-limiting toxicity (DLT) observation period. Dose Escalation Rules: If both cohorts at Dose Level 1 (golidocitinib + selinexor combinations) demonstrate acceptable tolerability per the SRC, golidocitinib is escalated to the higher dose in Dose Level 2. If either cohort at Dose Level 1 is deemed intolerable by the SRC, de-escalation to Dose Level 0 (baseline dose) is mandated. Following completion of all 4 cohorts in Phase Ib, the recommended dose (RP2D) will be determined.

Study Record Dates

• First Submitted: May 2, 2025
• First Posted: May 11, 2025
• Study Start: May 26, 2025
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2028
• Last Updated: May 30, 2025

Record last verified: 2025-05

Locations

CN (1)