Golidocitinib Combined With P-GemOx Plus PD-1 Inhibitor Versus P-GemOx Plus PD-1 Inhibitor in First-Line Newly Diagnosed Advanced or Non-Nasal Extranodal NK/T-Cell Lymphoma

Official title

A Randomized Controlled Multicenter Phase 2 Clinical Trial of Golidocitinib Combined With P-GemOx Plus PD-1 Inhibitor Versus P-GemOx Plus PD-1 Inhibitor in the Treatment of First-Line Newly Diagnosed Advanced Extranodal NK/T-Cell Lymphoma (ENKTL) or Non-Nasal Extranodal NK/T-Cell Lymphoma (ENKTL)

Overview

This is a multicenter, randomized, Phase 2 clinical trial designed to evaluate the efficacy and safety of golidocitinib combined with the P-GemOx (pegaspargase + gemcitabine + oxaliplatin) regimen plus PD-1 inhibitor, compared with P-GemOx plus PD-1 inhibitor alone, in participants with first-line newly diagnosed advanced (Stage III-IV) or non-nasal extranodal natural killer/T-cell lymphoma (ENKTL). Eligible participants will be randomly assigned 1:1 to two groups: Experimental group: Golidocitinib (150 mg orally once daily, Days 1-21 per 21-day cycle) + P-GemOx (pegaspargase 2000 U/m² on Day 2; gemcitabine 1000 mg/m² on Day 1; oxaliplatin 100 mg/m² on Day 1, per 21-day cycle) + PD-1 inhibitor (200 mg intravenously on Day 1 per 21-day cycle). Control group: P-GemOx + PD-1 inhibitor (same dosage/schedule as the experimental group, without golidocitinib). All participants will receive 6 cycles of induction therapy. Those achieving CR or partial response (PR) after induction will receive maintenance therapy for 1 year: the experimental group will continue golidocitinib + PD-1 inhibitor, while the control group will receive PD-1 inhibitor alone (both per 21-day cycles). The primary outcome is the complete response rate (CRR) after 6 induction cycles (assessed per the 2014 Lugano Classification for Lymphoma). Secondary outcomes include overall response rate (ORR), 2-year progression-free survival (PFS), 2-year overall survival (OS), and the incidence of treatment-related adverse events (graded per NCI-CTCAE Version 5.0). 40 participants will be enrolled across multiple Chinese medical centers. This Phase 2 trial will provide preliminary evidence to determine whether the golidocitinib combination regimen is a safe and effective first-line option for advanced or non-nasal ENKTL.

Interventions

• Drug Golidocitinib in combination with P-GEMOX and PD-1 inhibitor
  Participants receive this combination for 6 cycles of induction therapy. Those achieving complete response (CR) or partial response (PR) post-induction will continue maintenance therapy with golidocitinib plus PD-1 inhibitor (same dosage and administration schedule) for 1 year, or until disease progression, unacceptable toxicity, or voluntary withdrawal from the study. This regimen is designed to target the STAT3 signaling pathway (via golidocitinib) while combining cytotoxic chemotherapy (P-GEM
• Drug PD-1 inhibitor in combination with P-GEMOX
  Participants receive this combined regimen for 6 cycles of induction therapy. For those achieving complete response (CR) or partial response (PR) post-induction, maintenance therapy is continued with PD-1 inhibitor alone (same 200 mg intravenous dose on Day 1 of each 21-day cycle) for 1 year, or until disease progression, unacceptable treatment-related toxicity, or study discontinuation. This regimen represents a currently established first-line therapeutic option for advanced/non-nasal ENKTL, s

Primary outcome measures

• Complete Response Rate (CRR) After 6 Cycles of Induction Therapy [Time frame: Within 21 days after the completion of the 6th cycle of induction therapy (Each cycle is 21 days)]

Secondary outcome measures (4)

• Overall Response Rate (ORR) After 6 Cycles of Induction Therapy [Time frame: Within 21 days after the completion of the 6th cycle of induction therapy At the end of Cycle 1 (each cycle is 28 days)]
• 2-Year Progression-Free Survival (PFS) [Time frame: Up to 2 years after randomization]
• 2-Year Overall Survival (OS) [Time frame: Up to 2 years after randomization]
• Incidence of Treatment-Related Adverse Events (TRAE) [Time frame: From the first dose of study intervention to 30 days after the last dose of study intervention]

Eligibility criteria

Inclusion criteria

• Voluntarily provides written informed consent (ICF) prior to any study procedures.
• Aged 18-70 years (inclusive), regardless of sex.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed extranodal NK/T-cell lymphoma (ENKTL), staged as Stage III-IV or non-nasal ENKTL (per 2016 WHO Classification of Hematopoietic and Lymphoid Tumors).
• At least one measurable/evaluable lesion (per 2014 Lugano Classification: measurable lesion ≥1.5 cm in longest diameter + ≥1.0 cm in shortest diameter; evaluable lesion with FDG uptake higher than liver on PET/CT).
• Treatment-naive (no prior anti-cancer therapy for ENKTL).
• Adequate organ function:

AST/ALT ≤2.5×upper limit of normal (ULN); Total bilirubin (TBIL) ≤1.5×ULN; Serum creatinine <1.5×ULN or creatinine clearance (CrCl, via Cockcroft-Gault formula) ≥60 mL/min.

• Reproductive-aged females have a negative pregnancy test at screening; all participants use effective contraception during the study and for 12 months after the last dose.
• Expected survival ≥6 months.

Exclusion criteria

• Complicated by hemophagocytic lymphohistiocytosis (HLH) or aggressive NK-cell leukemia.
• Contraindication to golidocitinib, PD-1 inhibitor, or any component of the P-GEMOX regimen.
• Lymphoma involvement of the central nervous system (CNS).
• Major surgery (excluding diagnostic biopsy) within 4 weeks prior to study treatment initiation.
• History of other malignant tumors (except curatively treated in situ cancers, e.g., cervical carcinoma in situ) within 5 years.
• Uncontrolled severe comorbidities (e.g., NYHA Class II+ heart failure, unstable angina, myocardial infarction within 1 year, uncontrolled arrhythmias).
• Active bleeding (e.g., gastrointestinal hemorrhage, cerebral hemorrhage).
• Uncontrolled infection (requiring parenteral anti-infective therapy) within 7 days prior to study treatment.
• Active hepatitis B/C: HBsAg+/HBcAb+ with HBV-DNA >2500 copies/mL (or 500 IU/mL); HCV antibody+ with positive HCV-RNA.
• HIV infection or acquired immunodeficiency syndrome (AIDS).
• Conditions impairing drug absorption (e.g., inability to swallow tablets, malabsorption syndrome).
• Pregnant/lactating females, or reproductive-aged participants refusing contraception.
• Psychiatric illness precluding informed consent or study compliance.
• Other conditions deemed unsuitable for enrollment by the investigator.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07385989 · 2025-SR-682

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗