A Phase 1, First-in-human Study of JNJ-80948543, a T-cell Redirecting Antibody, in Participants With NHL and CLL
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 167
- 试验地点
- 29
- 主要终点
- Number of Participants with Dose-limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to characterize safety and to determine the putative recommended Phase 2 dose(s) (RP2D[s]), optimal dosing schedule(s) and route(s) of administration of JNJ-80948543 in Part A (Dose Escalation) and to further characterize the safety of JNJ-80948543 at the putative RP2D(s) in Part B (Cohort Expansion).
研究设计
- 研究类型
- 干预性
- 分配方式
- 非随机
- 干预模型
- 序贯
- 主要目的
- 治疗
- 盲法
- 开放（无盲法）
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
- Histologic documentation of disease: B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) requiring therapy.
- All participants must have relapsed or refractory disease with no other approved therapies available that would be more appropriate in the investigator's judgment.
- B-cell NHL as defined per the 2016 world health organization (WHO) classification. In addition, the following disease-specific criteria outlined below must be met:
- If diffuse large B-cell lymphoma (DLBCL) or other high-Grade B-cell lymphoma: Received, or not eligible for high-dose chemotherapy and autologous stem cell transplantation with curative intent or deemed not eligible or fit for an alternative 2nd line therapy. Participants may be eligible if relapsing after chimeric antigen receptors (CAR-T) cell treatment or while waiting for a CAR-T cell treatment.
- If transformed lymphoma from low Grade B-cell malignancies: Received or not a candidate for an approved first-line regimen for DLBCL and received or not eligible for high-dose chemotherapy and autologous stem cell transplantation with curative intent.
- If follicular lymphoma (FL) (all grades): Previously treated with a minimum of 2 prior lines of systemic therapy, with at least one prior line containing an anti-CD20 antibody.
- If mantle cell lymphoma (MCL), marginal zone lymphoma (MZL) (including nodal, extranodal/MALT, and splenic MZL subtypes): Previously treated with at least 2 lines of systemic therapy. H.pylori-positive gastric MALT lymphoma must have failed prior H. pylori eradication therapy as one of their prior lines .
- Waldenstrom macroglobulinemia (WM): Previously treated with at least 1 line of systemic therapy.
- small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL/SLL): Relapsed or refractory with at least 2 prior lines of therapy, including a Bruton tyrosine kinase inhibitor (BTK) inhibitor or a BCL2 inhibitor, if eligible. In addition for part B Participants must have measurable disease as defined by the appropriate disease response criteria
- Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0 or 1
- Cardiac parameters within the following range: corrected QT interval (QTc intervals corrected using Fridericia's formula [QTcF]) less than or equal to (<=) 480 milliseconds based on the average of triplicate assessments performed no more than 5 (plus minus [+-] 3) minutes apart
- A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test (beta- human chorionic gonadotropin) at screening and must agree to further serum or urine pregnancy tests prior to the first dose, during the study and until 3 months after the last dose of study treatment
- A female participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study treatment
排除标准
- Known active central nervous system (CNS) involvement; Lymphoma with CNS involvement may be allowed in pharmacokinetic/ pharmacodynamic (PK/PD) and expansion cohorts if approved by the study evaluation team (SET)
- Prior solid-organ transplantation
- Autoimmune or inflammatory disease requiring systemic steroids or other immunosuppressive agents (example, methotrexate or tacrolimus) within 1 year prior to first dose of study drug
- Toxicity from prior anticancer therapy has not resolved to baseline levels or to Grade <= 1 (except alopecia, vitiligo, peripheral neuropathy, or endocrinopathies that are stable on hormone replacement, which may be Grade 2)
- Clinically significant pulmonary compromise, particularly the need for supplemental oxygen use to maintain adequate oxygenation
研究组 & 干预措施
Part B: Cohort Expansion
Participants will receive JNJ-80948543 by SC or IV administration.
干预措施: JNJ-80948543 (Drug)
Part A: Dose Escalation
Participants will receive JNJ-80948543 either by subcutaneous (SC) or intravenous (IV) administration to determine the putative recommended Phase 2 dose (RP2D) dosing schedule(s) and route(s) of administration based on safety, pharmacokinetic, pharmacodynamic, and preliminary assessment of efficacy across several dose regimens.
干预措施: JNJ-80948543 (Drug)
结局指标
主要结局
Number of Participants with Dose-limiting Toxicity (DLT)
时间窗: Up to 4 Years 3 months
Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Number of Participants with AE by Severity
时间窗: Up to 4 Years 3 months
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Severity scale ranges from Grade 1 (Mild) to Grade 4 (Life-threatening). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded as per American Society for Transplantation and Cellular Therapy (ASTCT).
Number of Participants with Adverse Events (AEs)
时间窗: Up to 4 Years 3 months
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.
次要结局
- Time to Response (TTR)(Up to 4 Years 3 months)
- Serum Concentration of JNJ-80948543(Up to 4 Years 3 months)
- Number of Participants with Presence of Anti-Drug Antibodies of JNJ-80948543(Up to 4 Years 3 months)
- Overall Response Rate (ORR)(Up to 4 Years 3 months)
- Rate of VGPR or Better for Participants with Waldenstrom Macroglobulinemia (WM)(Up to 4 Years 3 months)
- Duration of Response (DOR)(Up to 4 Years 3 months)
- Complete Response (CR) Rate(Up to 4 Years 3 months)
研究者
研究点 (29)
标识符
- NCT 编号
- NCT05424822
- 其他研究编号
- CR109174, 2022-000685-18, 80948543LYM1001, 2023-504187-42-00, 2023
日期
- 首次提交
- (4年前)
- 首次发布
- (4年前)
- 主要完成日期
- (11个月前)
- 研究完成日期
- (10个月后)
- 最近核实
- (29天前)
- 最近更新
- (前天)
监管与共享
- FDA 监管药物
- 是
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 是
- 是否有结果
- 否
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu