2023-504802-12-00招募中2 期
A Phase 1/2, Open-Label, Dose-Escalation Trial of GEN3013 in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Genmab A/S
- 入组人数
- 395
- 试验地点
- 41
- 主要终点
- Escalation End Points: - Dose limiting toxicity - Adverse events
研究概览
简要总结
Escalation Phase:
- Determine maximum tolerated dose and recommended phase 2 dose Expansion Phase:
- To evaluate clinical efficacy as determined by Lugano criteria Optimization part:
- to determine whether an alternative priming/intermediate dose regimen may reduce CRS risk
研究设计
- 分配方式
- Non-randomized
- 主要目的
- Optimization Part
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Patient must be 18 years of age or older (for expansion: In countries where the legal age is 21 years of age; only patients 21 years of age or older are eligible)
- •Documented CD20+ mature non-Hodgkin B-cell lymphoma according to WHO classification
- •Relapsed, progressive and/or refractory disease (Cheson et al., 2007) following treatment with an anti-CD20 monoclonal antibody
- •Patients must have received at least 2 prior lines of therapy
- •Patients must have measurable disease by imaging
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or
- •For MCL: ECOG PS <2 required for participation.
- •For the optimization part, patients must have R/R DLBCL, or FL grades 1-3A, or MCL (according to cohort).
排除标准
- •Primary central nervous system (CNS) lymphoma or known CNS involvement by lymphoma
- •AST, and/or ALT > 3 x upper limit of normal
- •Total bilirubin > 1.5 x upper limit of normal
- •Creatinine clearance < 45 mL/min
- •Known clinically significant cardiac disease, including: a. Onset of unstable angina pectoris within 6 months of signing ICF b. Acute myocardial infarction within 6 months of signing ICF c. Congestive heart failure (grade III or IV as classified by the New York Heart Association and/or known decrease ejection fraction of < 45%
- •Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrolment or within the previous 2 weeks prior to the first dose of epcoritamab, including COVID-19 infection.
- •Eligible for curative salvage therapy with high dose therapy followed by stem cell rescue
- •Active hepatitis B (DNA PCR-positive) or hepatitis C (RNA PCR positive infection). Subjects with evidence of prior HBV but who are PCRnegative are permitted in the trial but should receive prophylactic antiviral therapy.
- •Known human immunodeficiency virus (HIV) infection.
- •Exposed to live or live attenuated vaccine within 4 weeks prior to signing ICF
- •Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to first GEN3013 administration
- •Autologous HSCT within 100 days prior to first GEN3013 administration, or any prior allogeneic HSCT or solid organ transplantation
- •Contraindication to all uric acid lowering agents
结局指标
主要结局
Escalation End Points: - Dose limiting toxicity - Adverse events
Escalation End Points: - Dose limiting toxicity - Adverse events
Expansion End Points: - Overall response rate (ORR) determined by Lugano criteria as assessed by independent review committee (IRC)
Expansion End Points: - Overall response rate (ORR) determined by Lugano criteria as assessed by independent review committee (IRC)
Optimization End Points: - Adverse events; Rating of ≥ Grade 2 CRS events
Optimization End Points: - Adverse events; Rating of ≥ Grade 2 CRS events
次要结局
- Escalation End Points: - Cytokine measures - Laboratory parameters (biochemistry, hematology including immunophenotyping for absolute T-cell and B-cell counts as well as Tcell activation and exhaustion markers) - PK parameters (clearance, volume of distribution and area-under-the concentration- time curve (AUC0-Clast and AUC0-∞), maximum concentration (Cmax), time of Cmax (Tmax), pre dose values, and halflife)
- Escalation End Points: - Immunogenicity of GEN3013 - Anti-lymphoma activity, i.e. resolution of constitutional symptoms, reduction in tumor size, objective and best response - Duration of response - Progression free survival - Time to next anti-lymphoma therapy - Overall survival
- Expansion Efficacy End Points per IRC and Optimization Efficacy End Points per Investigator: - Duration of response (DOR) determined by Lugano criteria - Complete response (CR) rate determined by Lugano criteria - Duration of CR (DoCR) by Lugano criteria - Progression-free survival (PFS) determined by Lugano criteria - Time to response (TTR) determined by Lugano criteria
- Expansion Efficacy End Points per IRC and Optimization Efficacy End Points per Investigator: - Objective and best response rate determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) - PFS determined by LYRIC - DOR determined by LYRIC - DoCR determined by LYRIC - TTR determined by LYRIC - Overall survival (OS)
- Expansion Efficacy End Points per IRC and Optimization Efficacy End Points per Investigator: - Time to next (anti-lymphoma) therapy (TTNT) - Rate of MRD negativity - Safety (i.e., adverse events, laboratory parameters, hospitalizations, and cytokine measures)
- Expansion Efficacy End Points per IRC and Optimization Efficacy End Points per Investigator: - PK parameters (clearance, volume of distribution, Cmax, Tmax, trough concentrations, and half-life) and incidence of ADAs to GEN3013 - Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy – Lymphoma (FACT-Lym)
- Expansion Efficacy End Points per IRC and Optimization Efficacy End Points per Investigator: - Rate of ≥ Grade 2 CRS events and all grade CRS events following first full dose Rate of ≥ Grade 2 CRS events and all grade CRS events overall
研究者
Clinical Trial Information
Scientific
Genmab A/S
研究点 (41)
Loading locations...
相似试验
进行中（未招募）
1 期
A Phase 1/2 Study of OBI-992 in Subjects With Advanced Solid TumorsAdvanced Solid TumorNCT06480240OBI Pharma, Inc117
撤回
1 期
Pharmacokinetics, Safety, and Efficacy of Brigatinib Monotherapy in Pediatric and Young Adult Participants With ALK+ Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumors or Other Solid TumorsAnaplastic Lymphoma Kinase Positive (ALK +) Anaplastic Large Cell LymphomaInflammatory Myofibroblastic TumorsSolid TumorsNCT04260009Takeda
招募中
1 期
A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 MutationMixed Lineage Acute LeukemiaAcute Leukemia of Ambiguous LineageAcute Lymphoblastic LeukemiaMixed Phenotype Acute LeukemiaAcute Myeloid LeukemiaNCT04065399Syndax Pharmaceuticals447
招募中
1 期
Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-DegraderB-cell MalignancyNon-Hodgkin LymphomaChronic Lymphocytic Leukemia/Small Lymphocytic LymphomaMarginal Zone LymphomaDLBCL UnclassifiableRichter's TransformationMantle Cell LymphomaFollicular LymphomaWaldenström MacroglobulinemiaNCT05294731BeiGene146
已完成
1 期
A Phase 1/2 Trial of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Patients With ER+/HER2- Locally Advanced or Metastatic Breast CancerBreast CancerNCT04072952Arvinas Estrogen Receptor, Inc.217