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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Golidocitinib + P-GemOx + PD-1 Inhibitor | Experimental | Golidocitinib (150 mg orally once daily, Days 1-21) Pegaspargase (2000 U/m² intravenously, Day 2) Gemcitabine (1000 mg/m² intravenously, Day 1) Oxaliplatin (100 mg/m² intravenously, Day 1) PD-1 inhibitor (200 mg intravenously, Day 1) Participants receive 6 cycles of induction therapy; those achieving complete response (CR) or partial response (PR) will continue maintenance therapy (Golidocitinib + PD-1 inhibitor, same dosage/schedule) for 1 year or until disease progression. |
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| P-GemOx + PD-1 Inhibitor | Active Comparator | Pegaspargase (2000 U/m² intravenously, Day 2) Gemcitabine (1000 mg/m² intravenously, Day 1) Oxaliplatin (100 mg/m² intravenously, Day 1) PD-1 inhibitor (200 mg intravenously, Day 1) Participants receive 6 cycles of induction therapy; those achieving complete response (CR) or partial response (PR) will continue maintenance therapy (PD-1 inhibitor alone, same dosage/schedule) for 1 year or until disease progression. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Golidocitinib in combination with P-GEMOX and PD-1 inhibitor | Drug | 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-GEMOX) and immune checkpoint inhibition (PD-1 inhibitor) for synergistic anti-lymphoma activity. |
| Measure | Description | Time Frame |
|---|---|---|
| Complete Response Rate (CRR) After 6 Cycles of Induction Therapy | The proportion of evaluable participants who achieve complete response (CR) following 6 cycles of induction therapy. CR is defined in accordance with the 2014 Lugano Classification for Lymphoma: this requires the complete disappearance of all measurable/evaluable lymphoma lesions, resolution of all disease-related clinical symptoms, and normalization of imaging findings (e.g., no residual measurable disease on CT/MRI, and no metabolically active disease on FDG-PET/CT). The analysis population is restricted to participants who complete at least 4 cycles of induction therapy and have available post-treatment efficacy assessment data. | Within 21 days after the completion of the 6th cycle of induction therapy (Each cycle is 21 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) After 6 Cycles of Induction Therapy | The proportion of evaluable participants who achieve objective response (defined as complete response [CR] or partial response [PR]) following 6 cycles of induction therapy. Response assessment adheres to the 2014 Lugano Classification for Lymphoma: PR requires a ≥50% reduction in the sum of the longest diameters of measurable lesions, with no new lesions or progression of existing non-measurable disease. The analysis population includes participants who complete at least 4 induction cycles and have available post-treatment efficacy evaluation data. |
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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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wei Xu | Contact | 13951699449 | xuwei10000@hotmail.com |
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| PD-1 inhibitor in combination with P-GEMOX | Drug | 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, serving as the active comparator for evaluating the added benefit of golidocitinib in the experimental arm. |
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| 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) | The duration from randomization to the first occurrence of disease progression (per the 2014 Lugano Classification) or death from any cause. PFS will be estimated using the Kaplan-Meier method, and between-arm comparisons will be conducted via the log-rank test. Participants without progression or death at the end of follow-up will be censored at their last documented disease-evaluation date. | Up to 2 years after randomization |
| 2-Year Overall Survival (OS) | The duration from randomization to death from any cause. OS will be estimated using the Kaplan-Meier method, with between-arm comparisons performed using the log-rank test. Participants who remain alive at the 2-year follow-up endpoint will be censored at their last confirmed survival date. | Up to 2 years after randomization |
| Incidence of Treatment-Related Adverse Events (TRAE) | The proportion of participants experiencing any treatment-related adverse event, graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. This includes the incidence of grade 3-4 TRAEs and serious adverse events (SAEs; defined as events that are life-threatening, require hospitalization, result in persistent disability, or are fatal). | From the first dose of study intervention to 30 days after the last dose of study intervention |
| ID | Term |
|---|---|
| D054391 | Lymphoma, Extranodal NK-T-Cell |
| ID | Term |
|---|---|
| D016399 | Lymphoma, T-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000082082 | Immune Checkpoint Inhibitors |
| ID | Term |
|---|---|
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000074322 | Antineoplastic Agents, Immunological |
| D000970 | Antineoplastic Agents |
| D045506 | Therapeutic Uses |
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