An Open-label, Multicenter, Phase 1/1b Dose Escalation Study Evaluating the Pharmacokinetics, Safety, Tolerability, and Preliminary Efficacy of DCDS0780A, Alone or in Combination With Rituximab, or Obinutuzumab, in Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 7
- 主要终点
- Number of Participants with Adverse Events
研究概览
简要总结
This open-label, multicenter, Phase 1/1b study will evaluate the safety, tolerability, and pharmacokinetics of increasing doses of DCDS0780A in participants with relapsed or refractory B-cell non-Hodgkin's lymphoma. In the combination portion of the study, the safety and tolerability of DCDS0780A in combination with rituximab or obinutuzumab will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Life expectancy of at least 12 weeks
- •Histologically confirmed B-cell non-Hodgkin's lymphoma that has relapsed after or failed to respond to at least one prior treatment regimen and for which no suitable therapy of curative intent or higher priority exists
- •A clinical indication for treatment as determined by the investigator
- •Availability of archival or freshly collected tumor tissue before study enrollment
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Fasting (greater than or equal to [>=] 8 hours) glucose less than or equal to (<=) 160 milligrams per deciliter (mg/dL)
- •Participants requiring anti-diabetic medications must be on a stable dose and regimen for >=4 weeks
- •Adequate hematologic function without growth factor or transfusion support
- •For women who are not postmenopausal (>= 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods as specified in protocol
- •For men: agreement to remain abstinent or use a condom plus an additional contraceptive method as specified in protocol
排除标准
- •Prior use of any monoclonal antibody or antibody-drug conjugate within 4 weeks before Cycle 1, Day 1
- •Treatment with radiotherapy, any chemotherapeutic agent, systemic steroids used as an anti-neoplastic agent, or any other investigational anti-cancer agent within 2 weeks prior to Cycle 1, Day 1
- •Completion of autologous stem cell transplant within 100 days prior to Cycle 1, Day 1
- •Prior allogeneic stem cell transplant
- •Current or history of CNS lymphoma
- •Current Grade greater than (>) 1 toxicity (except alopecia and anorexia) from prior therapy
- •Current Grade >1 peripheral neuropathy from any cause
- •Glycosylated hemoglobin (HbA1c) >=7.5 percent (%)
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
- •Prior irradiation to lung fields
- •Clinically significant pulmonary disease
- •Recent major surgery within 4 weeks prior to Cycle 1, Day 1, other than superficial lymph node biopsies for diagnosis
- •Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- •Presence of positive test results for hepatitis B (hepatitis B surface antigen [HbsAg] and/or total hepatitis B core antibody [anti-HBc]) or hepatitis C (hepatitis C virus [HCV] antibody)
- •Known history of human immunodeficiency virus (HIV) seropositive status
- •Women who are pregnant or lactating or intending to become pregnant during the study
- •Any abnormal laboratory values as specified in protocol
- •Requirement for any excluded medication as specified in protocol
- •History of other malignancy that could affect compliance with the protocol or interpretation of results
- •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications, including inadequately controlled diabetes or significant cardiovascular disease
- •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 requiring treatment with intravenous antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1
- •Participants in Phase 1b Stage Only: Vaccination with live vaccines within 6 months before Cycle 1, Day 1
研究组 & 干预措施
DCDS0780A + Obinutuzumab
Participants will receive escalating doses of DCDS0780A on Day 2 of Cycles 1 and 2, and from Cycle 3 onwards on Day 1 of each 21-day cycle in combination with obinutuzumab at a dose of 1000 milligrams (mg) as intravenous infusion on Days 1, 8, and 15 of Cycle 1, and from Cycle 2 onwards on Day 1 of each 21-day cycle up to approximately 1 year or until disease progression or unacceptable toxicity (whichever comes first).
干预措施: Obinutuzumab (Drug)
DCDS0780A Monotherapy
Participants will receive escalating doses of DCDS0780A as intravenous infusion as monotherapy on Day 1 of each 21-day cycle up to approximately 1 year or until disease progression or unacceptable toxicity (whichever comes first).
干预措施: DCDS0780A (Drug)
DCDS0780A + Rituximab
Participants will receive escalating doses of DCDS0780A on Day 2 of Cycles 1 and 2, and from Cycle 3 onwards on Day 1 of each 21-day cycle in combination with rituximab at a dose of 375 milligrams per square meter (mg/m^2) of body surface area as intravenous infusion on Day 1 of each 21-day cycle up to approximately 1 year or until disease progression or unacceptable toxicity (whichever comes first).
干预措施: DCDS0780A (Drug)
DCDS0780A + Rituximab
Participants will receive escalating doses of DCDS0780A on Day 2 of Cycles 1 and 2, and from Cycle 3 onwards on Day 1 of each 21-day cycle in combination with rituximab at a dose of 375 milligrams per square meter (mg/m^2) of body surface area as intravenous infusion on Day 1 of each 21-day cycle up to approximately 1 year or until disease progression or unacceptable toxicity (whichever comes first).
干预措施: Rituximab (Drug)
DCDS0780A + Obinutuzumab
Participants will receive escalating doses of DCDS0780A on Day 2 of Cycles 1 and 2, and from Cycle 3 onwards on Day 1 of each 21-day cycle in combination with obinutuzumab at a dose of 1000 milligrams (mg) as intravenous infusion on Days 1, 8, and 15 of Cycle 1, and from Cycle 2 onwards on Day 1 of each 21-day cycle up to approximately 1 year or until disease progression or unacceptable toxicity (whichever comes first).
干预措施: DCDS0780A (Drug)
结局指标
主要结局
Number of Participants with Adverse Events
时间窗: Baseline up to 30 days after the last dose of study drug (up to 1 year)
Recommended Phase 2 Dose (RP2D) of DCDS0780A
时间窗: Days 1 to 21
Percentage of Participants with Dose-Limiting Toxicities
时间窗: Days 1 to 21
Maximum Tolerated Dose (MTD) of DCDS0780A
时间窗: Days 1 to 21
次要结局
- Time to CD19+ B-Cell Count Recovery to Baseline Value(Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years))
- Maximum Observed Serum Concentration (Cmax) for DCDS0780A Total Antibody(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Area Under the Serum Concentration-Time Curve (AUC) for DCDS0780A Total Antibody(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Volume of Distribution Under Steady-State Conditions (Vss) of DCDS0780A Total Antibody(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Half-life (t1/2) of Unconjugated MMAE(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Half-life (t1/2) of acMMAE(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Volume of Distribution Under Steady-State Conditions (Vss) of acMMAE(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Change from Baseline in Intra-Patient Absolute Lymphocyte Counts(Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years))
- Duration of Response Assessed According to Lugano Classification(From the first occurrence of a documented objective response (CR or PR) to the time of relapse or death from any cause (up to 1 year))
- Total Clearance (CL) of DCDS0780A Total Antibody(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Half-life (t1/2) of DCDS0780A Total Antibody(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Maximum Observed Plasma Concentration (Cmax) for acMMAE(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Area Under the Plasma Concentration-Time Curve (AUC) for Unconjugated Monomethyl Auristatin E (MMAE)(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Percentage of Participants with Anti-DCDS0780A Antibodies(Baseline up to 2 to 4 months after last dose (up to 16 months))
- Relative Dose Intensity (DI) Calculated as Ratio of Amount of Drug Actually Administered to the Amount Planned(Baseline up to 1 year)
- Area Under the Plasma Concentration-Time Curve (AUC) for DCDS0780A Conjugate (Antibody-Conjugated Monomethyl Auristatin E [acMMAE])(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Total Clearance (CL) of acMMAE(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Maximum Observed Plasma Concentration (Cmax) for Unconjugated MMAE(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Obinutuzumab Serum Concentration(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Total Clearance (CL) of Unconjugated MMAE(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Volume of Distribution Under Steady-State Conditions (Vss) of Unconjugated MMAE(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Rituximab Serum Concentration(Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section))
- Absolute Lymphocyte Count(Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years))
- Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) Assessed According to Lugano Classification(Baseline up to first occurrence of disease progression or death from any cause within 30 days after the last dose of study drug (up to 1 year))
- Progression-Free Survival (PFS) Assessed According to Lugano Classification(Baseline up to first occurrence of disease progression or death from any cause within 30 days after the last dose of study drug (up to 1 year))