GNC-038 injection for patients with relapsed or refractory NK/T-cell lymphoma

An Open, Multicenter, Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacokinetics, and Antitumor Activity of GNC-038 Injection in Relapsed or Refractory NK/ T-cell Lymphoma, AITL, and Other NHL

This study is testing a new injection called GNC-038 to see if it can safely help people with relapsed or hard-to-treat NK/T-cell lymphoma and other types of non-Hodgkin lymphoma.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 2 sites (Guangzhou, Guangdong and 1 other locations)
• Trial ID: NCT05627856 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of GNC-038, an injection treatment, for patients suffering from relapsed or refractory NK/T-cell lymphoma, vascular immunomother T-cell lymphoma, and other non-Hodgkin lymphomas. The trial is divided into two phases: Phase Ib focuses on determining the maximum tolerated dose (MTD), maximum administered dose (MAD), dose-limiting toxicity (DLT), and recommended Phase II dose (RP2D) while assessing pharmacokinetics and immunogenicity. Phase II will further evaluate the efficacy, safety, and tolerability of GNC-038 in a larger patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with histologically confirmed relapsed or refractory NK/T-cell lymphoma or vascular immunomother T-cell lymphoma.

Not a fit: Patients who have not previously received systemic 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 therapeutic option for patients with difficult-to-treat lymphomas.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, but this specific treatment is novel.

Eligibility criteria

Inclusion Criteria:

1. Subjects can understand the informed consent, voluntarily participate in and sign the informed consent.
2. No gender restriction.
3. Age: ≥18 and ≤75 years old.
4. Expected survival time ≥3 months.
5. Patients with histologically confirmed NK/T cell lymphoma or vascular immunomother T cell lymphoma.
6. Patients with relapsed/refractory NK/T cell lymphoma (R/R NKTCL) or relapsed/refractory vascular immunomother T cell lymphoma (AITL):

1) Patients with recurrent or refractory vascular immunomother T cell lymphoma after initial treatment.

2) Patients with NK/T cell lymphoma need to have received systematic therapy with asparaginase regimen in the past, and have received radiotherapy for single lesion recurrence or refractory treatment.

Difficult-to-treat definition: i) the curative effect of end-line treatment did not reach PR; Or ii) disease progression within 6 months after terminal line treatment.

7. In the screening period, there were measurable lesions (lymph node lesions with any length ≥1.5cm or exodal lesions with any length \> 1.0cm, all of which had metabolic activity).

8. Physical status score ECOG ≤2 points. 9. The adverse reactions of previous antitumor therapy were restored to CTCAE level 5.0 evaluation ≤ level 1 (except for indicators that the researchers considered might be related to the disease, such as anemia, and toxicities that the researchers judged to have no safety risk, such as hair loss, grade 2 peripheral neurotoxicity, stable hypothyroidism after hormone replacement therapy, etc.).

10. Organ function level before initial administration meets the following requirements: Bone marrow function: without blood transfusion within 7 days prior to screening, without G-CSF (without long-acting rising white needle within 2 weeks) and drug correction: Absolute neutrophil count (ANC) ≥1.0×109/L (≥0.5×109/L for subjects with bone marrow infiltration); Hemoglobin ≥80 g/L (≥70g/L for subjects with bone marrow infiltration); Platelet count ≥75×109/L; Liver function: total bilirubin ≤1.5 ULN (Gilbert's syndrome ≤3 ULN), transaminase (AST/ALT) ≤2.5 ULN (subjects with liver tumor invasive changes ≤5.0 ULN) within 7 days before screening without liver protection drugs; Renal function: creatinine (Cr) ≤1.5 ULN and creatinine clearance (Ccr) ≥50 ml/min (according to Cockcroft and Gault formula); Urine routine /24 hours urine protein quantification: qualitative urine protein ≤1+ (if qualitative urine protein ≥2+, 24 hours urine protein \< 1g can be included in the group); Cardiac function: left ventricular ejection fraction ≥50%; Coagulation function: fibrinogen ≥1.5g/L; Activated partial thrombin time (APTT) ≤1.5 ULN; Prothrombin time (PT) ≤1.5 ULN.

11. Fertile female subjects or fertile male subjects with partners must use highly effective contraception from 7 days prior to the first dose until 12 weeks after termination of treatment. A fertile female subject must have a negative serum/urine pregnancy test within 7 days prior to initial dosing.

12. Subject is able and willing to comply with visits, treatment plans, laboratory tests, and other study-related procedures as specified in the study protocol.

Exclusion Criteria:

1. According to NCI-CTCAE v5.0, it was defined as ≥ grade 3 pulmonary disease; Patients who currently have interstitial lung disease (ILD) (except those who previously had interstitial pneumonia and have recovered).
2. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
3. Active tuberculosis.
4. Patients with hemophagocytic syndrome.
5. Patients with lesions invading pulmonary great vessels.
6. Active patients with autoimmune diseases, such as: systemic lupus erythematosus, systemic treatment of psoriasis, rheumatoid arthritis, inflammatory bowel disease, and hashimoto's thyroiditis, etc., with the exception of type I diabetes, only replacement therapy can control the hypothyroidism, no systemic treatment of skin disease (e.g., vitiligo, psoriasis), B cells caused by autoimmune disease.
7. Non-melanoma skin cancer in situ, superficial bladder cancer in situ, cervical cancer in situ, gastrointestinal intramucosal cancer, breast cancer, localized prostate cancer and other malignant tumors that were combined with other malignant tumors within 5 years prior to the first administration of the drug, except those that the researchers thought could be included.
8. HBsAg positive or HBcAb positive, and HBV-DNA detection ≥ detection value lower limit (HBV-DNA detection in the normal range and regular use of anti-HBV drugs except patients); HCV antibody was positive and HCV-RNA≥ lower limit of detection value.
9. Poorly controlled hypertension (systolic blood pressure \&gt;160 mmHg or diastolic blood pressure \&gt;100 mmHg).
10. A history of severe cardiovascular and cerebrovascular diseases, including but not limited to:

    Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias and degree III atrioventricular block that require clinical intervention; Prolonged QT interval at rest (QTc \> 450 msec in men or 470 msec in women); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurring within 6 months prior to initial administration; Present with heart failure ≥II on the New York Heart Association (NYHA) cardiac function scale.
11. Patients with a history of allergy to recombinant humanized antibodies or to any excipient component of GNC-038.
12. Pregnant or breastfeeding women.
13. Patients with central nervous system invasion.
14. Patients who received major surgery within 28 days prior to drug administration in this study, or planned to undergo major surgery during the study period (except for procedures such as puncture or lymph node biopsy).
15. Previous recipients of organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
16. Autologous hematopoietic stem cell transplantation (Auto-HSCT) within 24 weeks before starting GNC-038 therapy.
17. Immunosuppressants are being used, including, but not limited to, cyclosporine, tacrolimus, etc. within 2 weeks prior to treatment with GNC-038.
18. Radiotherapy was received within 4 weeks prior to the initiation of GNC-038 therapy.
19. Received chemotherapy and small molecule targeted therapy within 2 weeks prior to treatment.
20. Received CAR-T therapy within 12 weeks prior to initiation of GNC-038 therapy.
21. Participants in any other clinical trial within 4 weeks prior to administration of this trial.
22. A history of immunodeficiency, including HIV positive testing, or other acquired, congenital immunodeficiency diseases.
23. Other conditions deemed unsuitable for participation in this clinical trial by the investigator.

Where this trial is running

Guangzhou, Guangdong and 1 other locations

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• Guangdong Provincial People's Hospital — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Wenyu Li, PHD — Guangdong Provincial People's Hospital
• Study coordinator: Sa Xiao, PHD

Conditions NK/T Cell Lymphoma; Vascular Immunomother T Cell Lymphoma; Non-Hodgkin Lymphoma