An Open, Multicenter, Phase Ib/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Tetra-specific Antibody GNC-038 Injection in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 5
- 主要终点
- Maximum tolerated dose (MTD) or Maximum dose (MAD)
研究概览
简要总结
To explore the safety and preliminary efficacy of GNC-038 in patients with relapsed or refractory NHL, and to determine the MTD and RP2D of GNC-038, or the MAD and DLT
详细描述
phase Ib: To explore the safety and preliminary efficacy of GNC-038 in patients with relapsed or refractory NHL, and to determine the MTD and RP2Dof GNC-038, or the MAD and DLT of GNC-038 if MTD is not reached, by intravenous infusion (IV, QW) once a week (2 weeks as a cycle) phase II To explore the efficacy of GNC-038 in patients with relapsed or refractory non-Hodgkin's lymphoma
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject is capable of understanding 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;
- •Patients with histologically confirmed non-Hodgkin's lymphoma;
- •Patients with relapsed or refractory non-Hodgkin's lymphoma (R/R NHL);
- •Presence of measurable lesions during the screening period (lymph node lesions with any long diameter ≥1.5 cm or extranodal lesions with any long diameter >1.0 cm);
- •ECOG performance status score ≤2;
- •Adverse reactions from prior anti-tumor treatment have recovered to ≤Grade 1 as per CTCAE 5.0 criteria;
- •Organ function levels meet the requirements 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 treatment discontinuation. 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.
排除标准
- •Pulmonary diseases classified as ≥Grade 3 according to NCI-CTCAE v5.0; patients currently diagnosed with interstitial lung disease (ILD);
- •Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
- •Active tuberculosis;
- •Patients with active autoimmune diseases;
- •History of other malignancies within 5 years prior to the first dose;
- •HBsAg-positive and/or HBcAb-positive with HBV-DNA levels ≥ the lower limit of detection; HCV antibody-positive with HCV-RNA levels ≥ the lower limit of detection; HIV antibody-positive;
- •Poorly controlled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg);
- •History of severe cardiovascular or cerebrovascular diseases;
- •Patients with a history of hypersensitivity to recombinant humanized antibodies or any excipients of GNC-038;
- •Pregnant or lactating women;
- •Patients with central nervous system involvement;
- •Major surgery within 28 days before the first dose of this study or planned major surgery during the study period;
- •Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
- •Autologous hematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks before initiating GNC-038 treatment;
- •Current use of immunosuppressive therapy;
- •Radiotherapy within 4 weeks before initiating GNC-038 treatment;
- •Chemotherapy or small-molecule targeted therapy within 2 weeks or 5 half-lives prior to treatment;
- •CAR-T therapy within 12 weeks before initiating GNC-038 treatment;
- •Use of any other investigational drug in a clinical trial within 4 weeks or 5 half-lives before the first dose of this study;
- •Any other condition deemed unsuitable for participation in this clinical trial by the investigator.
研究组 & 干预措施
Study treatment
Participants receive GNC-038 as intravenous infusion for the first cycle (2 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: GNC-038 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) or Maximum dose (MAD)
时间窗: Up to 14 days after the first dose
In the dose increment stage, the highest dose whose estimated DLT rate is closest to the target DLT rate but does not exceed the upper bound of the equivalent interval of DLT rate is selected as MTD.
Recommended dose for Phase II clinical studies (RP2D)
时间窗: Up to 14 days after the first dose
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of GNC-038.
Adverse Events during Treatment (TEAE)
时间窗: Up to approximately 24 months
TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of GNC-038. The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-038.
Dose limiting toxicity (DLT)
时间窗: Up to 14 days after the first dose
The incidence and severity of adverse events (TEAE) during treatment were graded according to the National Cancer Institute Standard for Common Terminology for Adverse Events (NCI-CTCAE, v5.0).
次要结局
- Adverse Events of Special Interest (AESI)(Up to approximately 24 months)
- AUC0-T(Up to approximately 24 months)
- disease control rate (DCR)(Up to approximately 24 months)
- Tmax(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)
- anti-drug antibody (ADA) in Ⅰa(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- AUC0-INF(Up to approximately 24 months)
- DOR (Duration of Response)(Up to approximately 24 months)
- progression-free survival (PFS)(Up to approximately 24 months)