NCT07101328招募中1 期
BAF_FRontier-1, A First-in-Human, Phase 1 Trial to Assess Safety, Tolerability, and Preliminary Efficacy of LY4152199, a B-cell Activation Factor Receptor (BAFF-R) T-Cell Engager Bispecific Antibody in Adult Participants With Previously Treated B-cell Malignancies
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 215
- 试验地点
- 96
- 主要终点
- Phase 1b - Overall Response Rate (ORR): Percentage of Participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR)
研究概览
简要总结
The purpose of this study is to find the best dose of the drug and measure the safety and efficacy of LY4152199 in participants with previously treated B-cell malignancies. Participants will have the option to continue taking LY4152199 until the study ends.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Must have a diagnosis of either follicular lymphoma or diffuse large B-cell lymphoma.
- •Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Estimated life expectancy of greater than or equal to (≥)12 weeks as judged by the Investigator.
- •Participants with select tumor types must have measurable or assessable disease as defined below:
- •Participants with lymphoma must have at least 1 bi-dimensionally measurable lesion or in the absence of measurable lymphadenopathy, documentation of bone marrow involvement.
- •Participants with Waldenstrom macroglobulinemia (WM) must have measurable disease, defined as the presence of serum IgM with a minimum IgM level of greater than (>)2 times (×) upper limit of normal (ULN) based on local laboratory testing.
- •Must be able to comply with inpatient/outpatient treatment, laboratory monitoring, and required clinic visits for the duration of trial participation.
- •Must have adequate organ function.
- •Phase 1 Dose Escalation (Cohort A) Participants - Must have histologically confirmed relapsed/refractory B-cell malignancy.
- •Phase 1 Dose Optimization (Cohort B) Participants
- •- Must have histologically confirmed relapsed/refractory diffuse large B-cell lymphoma (DLBCL) de novo or transformed from follicular lymphoma (FL).
排除标准
- •All Participants
- •Known or suspected peripheral blood involvement by malignant cells with an absolute lymphocyte count of greater than or equal to (≥) 5000 cells per microliter (μL).
- •Known or suspected central nervous system (CNS) involvement by systemic lymphoma.
- •Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
- •Any unresolved toxicities from prior therapy greater than National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade 2 at the time of starting trial treatment except for alopecia.
- •Autologous stem cell transplantation within 100 days of this study for post autologous transplant individuals.
- •Residual symptoms of neurotoxicity or cytopenias from prior chimeric antigen receptor T-cell therapy (CAR-T) or bispecifics. Exception: Cytopenia related to prior CAR-T or bispecifics allowed if they meet the adequate organ function criteria.
- •Known or suspected history of macrophage activation syndrome or hemophagocytic lymphohistiocytosis (HLH).
- •Active second malignancies, unless in remission, with life expectancy greater than 2 years with Sponsor approval.
- •History of autoimmune disease
- •Significant cardiovascular disease
- •Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection (except for fungal nail infection), or other clinically significant active disease process
- •Vaccination with a live vaccine within 4 weeks prior to signing informed consent form (ICF).
- •Have current or had a history of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins).
- •Prior treatment with B-cell activating factor receptor (BAFF-R) directed therapies (e.g., monoclonal antibody, CAR-T or bispecific antibody).
- •Pregnant and/or planning to breastfeed during the trial or within 90 days of the last dose of study intervention.
- •Known hypersensitivity to any component or excipient of LY4152199.
研究组 & 干预措施
Phase 1: Dose Escalation (Cohort A) - DLBCL and FL
Experimental
Escalating doses of LY4152199 administered intravenously (IV)
干预措施: LY4152199 - IV (Drug)
Phase 1: Dose Optimization (Cohort B1) - DLBCL
Experimental
Two or more doses of LY4152199 (evaluated during dose escalation) administered IV
干预措施: LY4152199 - IV (Drug)
Phase 1: Dose Optimization (Cohort B2) - FL
Experimental
Two or more doses of LY4152199 (evaluated during dose escalation) administered IV
干预措施: LY4152199 - IV (Drug)
结局指标
主要结局
Phase 1b - Overall Response Rate (ORR): Percentage of Participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR)
时间窗: Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy
Assessed by the Investigator per disease-specific response criteria as appropriate or death due to any cause, whichever occurs first
Phase 1 - Number of Participants with Dose Limiting Toxicities (DLT) of LY4152199
时间窗: Approximately 35 days
次要结局
- Phase 1a and 1b - Pharmacokinetics (PK): Area under the Concentration versus Time Curve (AUC) of LY4152199(Baseline up to approximately 91 weeks)
- Phase 1a and 1b - PK: Maximum Concentration (Cmax) of LY4152199(Baseline up to approximately 91 weeks)
- Phase 1a - Overall Response Rate (ORR): Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR)(Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy)
- Phase 1a and Ib - Duration of Response (DOR)(Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy)
- Phase 1a and Ib - Time to Response (TTR)(Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy)
- Phase 1a and Ib - Progression Free Survival (PFS)(Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy)
- Phase 1a and Ib - Disease Control Rate (DCR)(Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy)
- Phase 1 - Pharmacokinetics (PK): Area under the Concentration versus Time Curve (AUC) of LY4152199(Baseline up to approximately 91 weeks)
- Phase 1- PK: Maximum drug Concentration (Cmax) of LY4152199(Baseline up to approximately 91 weeks)
- Phase 1 - Duration of Response (DOR)(Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy)
- Phase 1 - Overall Response Rate (ORR): Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR)(Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy)
- Phase 1- Time to Response (TTR)(Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy)
- Phase 1 - Progression Free Survival (PFS)(Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy)
- Phase 1- Disease Control Rate (DCR)(Baseline up to approximately 4 years until disease progression or start of new anti-cancer therapy)
研究者
研究点 (96)
Loading locations...
相似试验
暂停
1 期
A Phase 1 Study of AMG 330 in Subjects With Myeloid MalignanciesRelapsed/Refractory AML, Minimal Residual Disease Positive AML, Myelodysplastic SyndromeJPRN-jRCT2071210044Contact Local256
暂停
1 期
Safety, Tolerability, PK, PD, and Efficacy of AMG 427 in Subjects With Relapsed/Refractory Acute Myeloid LeukemiaRelapsed/Refractory Acute Myeloid Leukemia (AML)JPRN-jRCT2031210152ocal Contact200
已完成
1 期
AMG 176 First in Human Trial in Participants With Relapsed or Refractory Multiple Myeloma and Participants With Relapsed or Refractory Acute Myeloid LeukemiaRelapsed or Refractory Multiple MyelomaRelapsed or Refractory Acute Myeloid LeukemiaJPRN-jRCT2080224749Amgen K.K.175
已完成
不适用
A phase 1 first-in-human study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of AMG232 in adult subjects with advanced solid tumors or multiple myelomasolide tumorentumor in the organsNL-OMON44939Amgen42
招募中
1 期
First-in-Human Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of the BTK Degrader, ABBV-101, in Participants with B-cell MalignanciesHematologic CancerJPRN-jRCT2031230249Satomi Natsuko128