A Study of GNC-035 in Relapsed or Refractory Non-Hodgkin 's Lymphoma and Other Hematological Malignancies

Официальное название

An Open, Multicenter, Phase I / II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics / Pharmacodynamics and Antitumor Activity of GNC-035 Tetra-specific Antibody Injection in Relapsed or Refractory Non-Hodgkin 's Lymphoma and Other Hematological Malignancies

Обзор

Phase I main objectives: To observe the safety and preliminary efficacy of GNC-035 in patients with relapsed/refractory non-Hodgkin lymphoma and other hematological malignancies, to determine the DLT and MTD, or MAD, and to determine RP2D. Phase II Main objective: To explore the efficacy of GNC-035 in patients with relapsed/refractory non-Hodgkin lymphoma and other hematological malignancies.

Вмешательства

• Препарат GNC-035
  GNC-035 was administered by intravenous infusion for 2 h-4 h, once a week ( IV, QW ), 3 weeks as a cycle.

Первичные конечные точки

• Phase I: Dose limiting toxicity (DLT) [Срок оценки: Up to 21 days after the first dose]
• Phase I: Maximum tolerated dose (MTD) [Срок оценки: Up to 21 days after the first dose]
• Phase I: Treatment-Emergent Adverse Event (TEAE) [Срок оценки: Up to approximately 24 months]
• Phase I: Recommended Phase II Dose (RP2D) [Срок оценки: Up to 21 days after the first dose]
• Phase II: Objective Response Rate (ORR) [Срок оценки: Up to approximately 24 months]

Вторичные конечные точки (12)

• Phase I: Objective Response Rate (ORR) [Срок оценки: Up to approximately 24 months]
• Progression-free survival (PFS) [Срок оценки: Up to approximately 24 months]
• Disease Control Rate (DCR) [Срок оценки: Up to approximately 24 months]
• Duration of Response (DOR) [Срок оценки: Up to approximately 24 months]
• Phase I: Complete Response (CR) [Срок оценки: Up to approximately 24 months]
• Treatment-Emergent Adverse Event (TEAE) [Срок оценки: Up to approximately 24 months]
• Phase I: Cmax [Срок оценки: Up to 21 days after the first dose]
• Phase I: Tmax [Срок оценки: Up to 21 days after the first dose]
• Phase I: AUC0-inf [Срок оценки: Up to 21 days after the first dose]
• Phase I: AUC0-T [Срок оценки: Up to 21 days after the first dose]
• Phase I: CL [Срок оценки: Up to 21 days after the first dose]
• Phase Ib: T1/2 [Срок оценки: Up to 21 days after the first dose]

Критерии участия

Критерии включения

• The subject is able to understand the informed consent form, voluntarily participates, and signs the informed consent form;
• No gender restrictions;
• Age: ≥18 years and ≤75 years;
• Expected survival time ≥3 months;
• Histologically or cytologically confirmed relapsed or refractory non-Hodgkin's lymphoma;
• For patients with relapsed or refractory non-Hodgkin's lymphoma, specifically including: Patients who have failed at least one line of standard therapy; Patients with relapsed or refractory disease judged by the investigator to have no other available or suitable treatment options;
• For non-Hodgkin's lymphoma, at least one measurable lesion meeting the Lugano response criteria must be present during the screening period;
• ECOG performance status score ≤2;
• Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
• Organ function levels meet the requirements within 7 days before the first dose;
• Female subjects of childbearing potential or male subjects with partners of childbearing potential must use highly effective contraception from 7 days before the first dose until 12 weeks after the last dose. Female subjects of childbearing potential must have a negative serum/urine pregnancy test within 7 days before the first dose;
• The subject has the ability and willingness to comply with the study protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

Критерии исключения

• Patients who have undergone major surgery within 28 days prior to the administration of this study or are scheduled for major surgery during the study period (major surgery is defined by the investigator);
• Pulmonary diseases classified as ≥Grade 3 according to NCI-CTCAE v5.0;
• Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
• Patients with active autoimmune diseases;
• History of other malignancies within 5 years prior to the first dose;
• Positive for human immunodeficiency virus (HIV) antibodies, active tuberculosis, active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection;
• Poorly controlled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg) despite medication;
• History of severe cardiovascular or cerebrovascular diseases;
• Patients with a history of hypersensitivity to recombinant humanized antibodies or any excipients of GNC-035;
• Pregnant or lactating women;
• Patients with central nervous system involvement;
• Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
• Autologous hematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks before initiating GNC-035 treatment;
• Current use of immunosuppressive therapy;
• Radiotherapy or macromolecular targeted therapy within 4 weeks before initiating GNC-035 treatment; chemotherapy or small-molecule targeted therapy within 2 weeks or 5 half-lives (whichever is shorter) before treatment;
• Anti-CD20 or anti-CD79b treatment within 4 weeks before initiating GNC-035 treatment with ongoing response;
• CAR-T therapy within 12 weeks before initiating GNC-035 treatment;
• Use of investigational drugs from other clinical trials within 4 weeks or 5 half-lives (whichever is shorter) before the administration of this study;
• Any other condition deemed unsuitable for participation in this clinical trial by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing Cancer Hospital — Пекин

Идентификаторы

NCT: NCT06066203 · GNC-035-104

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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