A Phase 1, First-in-human Study of JNJ-87801493 in Combination With CD3 T-Cell Engagers in Participants With Relapsed/Refractory B-cell Non-Hodgkin Lymphoid Malignancies (NHLs)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 70
- 试验地点
- 12
- 主要终点
- Part 1: Number of Participants with Dose Limiting Toxicity (DLTs)
研究概览
简要总结
The purpose of this study is to characterize safety and to determine the recommended phase 2 regimen (RP2R) for JNJ-87801493 in combination with T-cell engagers (TCEs) [Part A: Dose Escalation] and to further assess the safety of JNJ-87801493 at the RP2R in combination with TCEs [Part B: Dose Expansion].
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologic documentation of B-cell NHL. All participants in part 1 must have relapsed or refractory disease with no other approved therapies available that would be more appropriate in the investigator's judgment. In Part 2, participants with diffuse large B-cell lymphoma (DLBCL) or other high-grade B cell lymphoma and participants with transformed lymphoma from low-grade B cell malignancies who relapsed or failed to respond to only one prior systemic treatment regimen can be included
- •Part 1 participants must have evaluable or measurable disease and Part 2 participants must have measurable disease; all as defined by the Lugano criteria for non-Hodgkin lymphoid malignancies (NHL) and the international workshop on Waldenstrom's Macroglobulinemia (IWWM-6) for WM
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •Hematologic laboratory parameters must meet the required criterias and the values must be without a transfusion or growth factors for at least 7 days prior to the first dose of study drug
- •Participants of childbearing potential must have a negative highly sensitive serum pregnancy test (beta (β)-human chorionic gonadotropin) at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study.
排除标准
- •Known active central nervous system involvement (CNS) or leptomeningeal involvement. CNS involvement may be allowed in specific cohorts as determined by the Study Evaluation Team (SET)
- •Prior solid-organ transplantation
- •Prior treatment with JNJ-80948543 and/or JNJ-
- •In addition, history of known allergies, hypersensitivity, or intolerance to either JNJ-80948543, JNJ-75348780, or JNJ-87801493 or its excipients
- •Chemotherapy, targeted therapy, or immunotherapy within 2 weeks before the first dose of study treatment. For investigational agents where the half-life is known, there should be a treatment-free window of at least 2 weeks or 5 half-lives. For checkpoint blockade therapy (example, anti-programmed cell death protein-1 [anti-PD-1]), a washout period of up to 6 weeks may be considered
- •Malignancy diagnosis other than the disease under study within 1 year prior to screening. Exceptions are squamous and basal cell carcinoma of the skin, carcinoma in situ of the cervix and any malignancy that is considered cured or has minimal risk of recurrence within 1 year of first dose of the study drugs in the opinion of both the investigator and sponsor's medical monitor
- •Autoimmune or inflammatory disease requiring systemic corticosteroids or other immunosuppressive agents within 1 year prior to first dose of study treatment
- •Evidence of active viral, bacterial, or uncontrolled systemic fungal infection requiring systemic treatment within 7 days before the first dose of study treatment
- •Abnormal cardiac function
研究组 & 干预措施
Part 1: Dose escalation
Participants will receive one cycle of TCE monotherapy (step up dosing) with either JNJ-80948543 or JNJ-75348780 followed by initiation of combination therapy with JNJ-87801493 at least one week later.
干预措施: JNJ-80948543 (Drug)
Part 2:Dose expansion
Participants with specific B-cell NHL histologies will receive recommended phase 2 regimen (RP2R) of JNJ-87801493 with TCE as determined in Part 1.
干预措施: JNJ-87801493 (Drug)
Part 1: Dose escalation
Participants will receive one cycle of TCE monotherapy (step up dosing) with either JNJ-80948543 or JNJ-75348780 followed by initiation of combination therapy with JNJ-87801493 at least one week later.
干预措施: JNJ-75348780 (Drug)
Part 1: Dose escalation
Participants will receive one cycle of TCE monotherapy (step up dosing) with either JNJ-80948543 or JNJ-75348780 followed by initiation of combination therapy with JNJ-87801493 at least one week later.
干预措施: JNJ-87801493 (Drug)
Part 2:Dose expansion
Participants with specific B-cell NHL histologies will receive recommended phase 2 regimen (RP2R) of JNJ-87801493 with TCE as determined in Part 1.
干预措施: JNJ-75348780 (Drug)
Part 2:Dose expansion
Participants with specific B-cell NHL histologies will receive recommended phase 2 regimen (RP2R) of JNJ-87801493 with TCE as determined in Part 1.
干预措施: JNJ-80948543 (Drug)
结局指标
主要结局
Part 1: Number of Participants with Dose Limiting Toxicity (DLTs)
时间窗: Up to 2 years 7 months
Number of participants with DLTs will be reported. The DLTs are drug-related toxicities and are defined as any of the following: fatal toxicity, high grade non-hematologic toxicity, or hematologic toxicity
Part 1 and 2: Percentage of Participants with Adverse Events (AEs) by Severity
时间窗: Up to 2 years 7 months
An AE is any untoward medical occurrence in a clinical study participant administered an investigational or non-investigational product and it does not necessarily have a causal relationship with the investigational product. Severity for AEs will be specified as per: NCI-CTCAE grades which are Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (potentially life-threatening) and; American Society for Transplantation and Cellular Therapy (ASTCT) guidelines which is Grade 5 (death related to adverse event); Cytokine release syndrome (CRS) and associated neurologic toxicity events (immune effector cell-associated neurotoxicity syndrome events \[ICANS\]).
次要结局
- Number of Participants with Presence of Anti-JNJ-87801493, Anti-JNJ- 80948543 and Anti-JNJ-75348780 Antibodies(Up to 2 years 7 months)
- Overall Response as Assessed by the Investigator(Up to 2 years 7 months)
- Time to Response (TTR) as Assessed by the Investigator(Up to 2 years 7 months)
- Duration of Response (DOR) as Assessed by the Investigator(Up to 2 years 7 months)
- Serum Concentration for JNJ-87801493, JNJ-80948543 and JNJ-75348780(Up to 2 years 7 months)
- Apparent Volume of Distribution (V/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780(Up to 2 years 7 months)
- Area Under the Curve (AUCtau) for JNJ-87801493, JNJ-80948543 and JNJ-75348780(Up to 2 years 7 months)
- Minimum Serum Concentration (Cmin) for JNJ-87801493, JNJ-80948543 and JNJ-75348780(Up to 2 years 7 months)
- Maximum Serum Concentration (Cmax) for JNJ-87801493, JNJ-80948543 and JNJ-75348780(Up to 2 years 7 months)
- Area Under the Curve (AUC[0-t]) for JNJ-87801493, JNJ-80948543 and JNJ-75348780(Up to 2 years 7 months)
- Half-life (t1/2) for JNJ-87801493, JNJ-80948543 and JNJ-75348780(Up to 2 years 7 months)
- Time to Reach Cmax (Tmax) for JNJ-87801493, JNJ-80948543 and JNJ-75348780(Up to 2 years 7 months)
- Apparent Total Body Clearance (CL/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780(Up to 2 years 7 months)
- Complete Response (CR) as Assessed by the Investigator(Up to 2 years 7 months)
- Very Good Partial Response (VGPR) or better for Waldenström Macroglobulinemia (WM) Participants as Assessed by the Investigator(Up to 2 years 7 months)