A Phase I, Open-Label, Multicenter Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Efficacy of Glofitamab as Single Agent Administered After a Fixed, Single Dose Pretreatment of Obinutuzumab in Chinese Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 6
- 主要终点
- Percentage of Participants with Adverse Events (AEs)
研究概览
简要总结
This study will evaluate the pharmacokinetics, safety, tolerability, and efficacy of glofitamab as a single agent following a fixed single dose of obinutuzumab in Chinese patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have failed two or more lines of systemic therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically-confirmed DLBCL
- •Participants must have relapsed or failed to respond to at least two lines of prior systemic therapy (including at least one prior regimen containing anthracycline, and at least one containing an anti-CD20-directed therapy)
- •Participants must have measurable disease: at least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension; or at least one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 1 or 1
- •Adverse events from prior anti-cancer therapy must have resolved to Grade </=1
- •Adequate liver, hematological, and renal function
- •Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential
- •Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception as defined by the protocol, and agree to refrain from donating eggs during the treatment period and for at least 18 months after the final dose of obinutuzumab, 2 months after the final dose of glofitamab, and 3 months after the final dose of tocilizumab (if applicable)
- •Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception as defined by the protocol, and agree to refrain from donating sperm during the treatment period and for at least 3 months after the final dose of obinutuzumab, 4 months after the final dose of glofitamab, and 2 months after the final dose of tocilizumab (if applicable)
- •Reside in the People's Republic of China
排除标准
- •Richter's transformation
- •Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection within 4 weeks prior to first study treatment
- •Suspected or latent tuberculosis
- •Positive for HIV, hepatitis C (HCV), or hepatitis B (HBV)
- •Known or suspected chronic active Epstein-Barr virus infection
- •Known or suspected history of hemaphagocytic lymphohistiocytosis (HLH)
- •Prior treatment with systemic immunotherapeutic agents
- •History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents
- •Documented refractoriness to an obinutuzumab monotherapy-containing regimen
- •Treatment with standard radiotherapy, any chemotherapeutic agent, including CAR T therapy
- •Prior solid organ or allogenic stem cell transplantation
- •Autologous stem cell transplantation within 100 days prior to obinutuzumab infusion
- •Active autoimmune disease requiring treatment
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
- •History of confirmed progressive multifocal leukoencephalopathy (PML)
- •Current or past history of CNS lymphoma
- •Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
- •Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, and known autoimmune diseases
- •Major surgery or significant traumatic injury < 28 days prior to obinutuzumab infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
- •Another invasive malignancy in the last 2 years
- •Significant cardiovascular disease
- •Administration of a live, attenuated vaccine within 4 weeks before obinutizumab infusion, or anticipation that one will be required during the study
- •Systemic immunosuppresive medications
研究组 & 干预措施
R/R DLBCL
Participants will receive a fixed dose of obinutuzumab pre-treatment followed by glofitamab on Cycle 1 Days 8 and 15, then every 3 weeks (Q3W) from Cycles 2-12 (cycle length = 21 days).
干预措施: Obinutuzumab (Drug)
R/R DLBCL
Participants will receive a fixed dose of obinutuzumab pre-treatment followed by glofitamab on Cycle 1 Days 8 and 15, then every 3 weeks (Q3W) from Cycles 2-12 (cycle length = 21 days).
干预措施: Glofitamab (Drug)
R/R DLBCL
Participants will receive a fixed dose of obinutuzumab pre-treatment followed by glofitamab on Cycle 1 Days 8 and 15, then every 3 weeks (Q3W) from Cycles 2-12 (cycle length = 21 days).
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Percentage of Participants with Adverse Events (AEs)
时间窗: Up to 3.5 years
Serum Concentration of Glofitamab
时间窗: At pre-defined intervals up to 3.5 years
Total Exposure (AUC) of Glofitamab
时间窗: At pre-defined intervals up to 3.5 years
Maximum Serum Concentration (Cmax) of Glofitamab
时间窗: At pre-defined intervals up to 3.5 years
Minimum Serum Concentration (Cmin) of Glofitamab
时间窗: At pre-defined intervals up to 3.5 years
Clearance of Glofitamab
时间窗: At pre-defined intervals up to 3.5 years
Volume of Distribution at Steady State (Vss) of Glofitamab
时间窗: At pre-defined intervals up to 3.5 years
Half-life (T1/2) of Glofitamab
时间窗: At pre-defined intervals up to 3.5 years
Complete Response Rate (CRR) as Assessed by an Independent Review Committee (IRC)
时间窗: Up to 3.5 years
Percentage of Participants with Anti-Drug Antibodies (ADA)
时间窗: Up to 3.5 years
次要结局
- Investigator-Assessed CRR(Up to 3.5 years)
- Duration of Complete Response (CR) as Assessed by IRC and Investigator(Up to 3.5 years)
- Time to First Overall Response (TFOR) as Assessed by IRC and Investigator(Up to 3.5 years)
- Objective Response Rate (ORR) as Assessed by IRC(Up to 3.5 years)
- ORR as Assessed by Investigator(Up to 3.5 years)
- Duration of Objective Response (DOR) as Assessed by IRC and Investigator(Up to 3.5 years)
- Progression-Free Survival (PFS) as Determined by IRC and Investigator(Up to 3.5 years)
- Overall Survival (OS)(Up to 3.5 years)
- Time to First Complete Response (TFCR) as Assessed by IRC and Investigator(Up to 3.5 years)