NCT03589469已完成2 期
A Phase 2 Open-Label Single-Arm Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (LOTIS-2)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 145
- 试验地点
- 37
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
The purpose of this Phase 2 study is to evaluate the clinical efficacy and safety of Loncastuximab Tesirine (ADCT-402) in patients with relapsed or refractory Diffuse Large B-Cell Lymphoma.
详细描述
This is a Phase 2, multi-center, open-label, single-arm study of the efficacy and safety of loncastuximab tesirine used as monotherapy in patients with relapsed or refractory DLBCL. The study will enroll approximately 140 patients
Loncastuximab Tesirine is an antibody drug conjugate (ADC) composed of a humanized antibody directed against human cluster of differentiation 19 (CD19), stochastically conjugated through a cathepsin-cleavable linker to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Loncastuximab tesirine has been designed to target and kill CD19-expressing malignant B-cells.
A 2-stage design will be used in this clinical study, with an interim analysis for futility on the first 52 patients. If ≥10 patients respond (CR+PR), the study will proceed to complete full enrollment. Enrollment will continue during the interim analysis; however, further enrollment will be halted if futility is confirmed.
For each patient, the study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 3 weeks), and a Follow-up Period (approximately every 12 week visits for up to 3 years after treatment discontinuation).
Patients may continue treatment until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.
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
- •Male or female patient aged 18 years or older.
- •Pathologic diagnosis of DLBCL, as defined by the 2016 WHO classification, to include: DLBCL not otherwise specified; primary mediastinal large B-cell lymphoma; and high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
- •Relapsed or refractory disease following two or more multi-agent systemic treatment regimens
- •Patients who have received previous CD19-directed therapy must have a biopsy that shows CD19 protein expression after completion of the CD19-directed therapy.
- •Measurable disease as defined by the 2014 Lugano Classification
- •Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block or minimum 10 freshly cut unstained slides if block is not available
- •ECOG performance status 0-2
- •Adequate organ function
- •Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drug (C1D1) for women of childbearing potential
- •Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the patient receives his last dose of loncastuximab tesirine.
排除标准
- •Previous treatment with loncastuximab tesirine
- •Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody
- •Pathologic diagnosis of Burkitt lymphoma
- •Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary
- •Autologous stem cell transplant (ASCT) within 30 days prior to start of study drug (C1D1)
- •Allogeneic stem cell transplant (AlloSCT) within 60 days prior to start of study drug (C1D1)
- •Active graft-versus-host disease
- •Post-transplant lymphoproliferative disorders
- •Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease
- •Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV).
- •History of Stevens-Johnson syndrome or toxic epidermal necrolysis
- •Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease
- •Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
- •Breastfeeding or pregnant
- •Significant medical comorbidities
- •Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor
- •Use of any other experimental medication within 14 days prior to start of study drug (C1D1)
- •Planned live vaccine administration after starting study drug (C1D1)
- •Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events version 4.0 [CTCAE v4.0]) from acute non-hematologic toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening
- •Congenital long QT syndrome or a corrected QTcF interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block)
- •Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the patient inappropriate for study participation or put the patient at risk
研究组 & 干预措施
Loncastuximab tesirine
Experimental
Participants will receive loncastuximab tesirine as an IV infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg Q3W for 2 cycles, then 75 μg/kg Q3W for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.
干预措施: Loncastuximab tesirine (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Up to 21.5 months
ORR, as determined by central review according to the 2014 Lugano classification, defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR).
次要结局
- Complete Response (CR) Rate(Up to 39 months)
- Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests(Baseline up to 599 days)
- Apparent Volume of Distribution at Steady State (Vss) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199(Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose)
- Change From Baseline Score in the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS)(Baseline, Day 1 of Cycles 2 to 26 (cycle duration of 3 weeks), and end of treatment (up to 599 days))
- Overall Survival (OS)(Up to 43 months)
- Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)(Up to 599 days)
- Number of Participants With Clinically Significant Change From Baseline in Vital Signs(Baseline up to 599 days)
- Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199(Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose)
- Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199(Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose)
- Apparent Terminal Half-life (Thalf) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199(Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose)
- Duration of Response (DOR)(Up to 39 months)
- Progression-free Survival (PFS)(Up to 40 months)
- Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment(Baseline and end of treatment (up to 599 days))
- Apparent Clearance (CL) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199(Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose)
- Accumulation Index (AI) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199(Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose)
- Number of Participants With an Anti-drug Antibody (ADA) Response to Loncastuximab Tesirine(Up to 599 days)
- Relapse-free Survival (RFS)(Up to 39 months)
- Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECGs)(Baseline up to 599 days)
- Maximum Concentration (Cmax) of Loncastuximab Tesirine Conjugated Antibody, Total Antibody and Warhead SG3199(Cycles 1 and 2: Day 1 pre-dose, and at 0, 4, 168 and 336 hours post-dose; Cycle 3: Day 1 pre-dose and end of infusion)
- Change From Baseline Score in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) - Lymphoma Subscale (LymS)(Baseline, Day 1 of Cycles 2 to 25 (cycle duration of 3 weeks), and end of treatment (up to 599 days))
研究者
研究点 (37)
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