A Multi-Center, Phase 1, Open-Label, Dose-Escalation Study of ABBV-428, an Immunotherapy in Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 61
- 试验地点
- 15
- 主要终点
- Number of participants with adverse events
研究概览
简要总结
This is an open-label, Phase I, dose-escalation study to determine the recommended Phase 2 dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK) profile of ABBV-428 when administered as monotherapy or in combination with nivolumab in participants with advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have an advanced solid tumor that has progressed on standard therapies known to provide clinical benefit or the participants are intolerant to such therapies.
- •Participants have adequate bone marrow, renal, hepatic and coagulation function.
- •For all dose expansion arms, participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
- •Participants in combination therapy cohorts must have an advanced solid tumor where the use of nivolumab is standard therapy.
排除标准
- •Active or prior documented autoimmune disease in the last 2 years. Participants with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
- •Current or prior use of immunosuppressive medication within 14 days prior to the first dose (with certain exceptions).
- •History of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
- •Confirmed positive test results for human immunodeficiency virus (HIV), or participants with chronic or active hepatitis B or C. Participants who have a history of hepatitis B or C who have undetectable HBV DNA or HCV RNA after anti-viral therapy may be enrolled.
- •Prior grade greater than or equal to 3 immune-mediated neurotoxicity or pneumonitis (or any other unresolved or symptomatic adverse event in the last 3 months) while receiving immunotherapy.
- •Male participants who are considering fathering a child or donating sperm during the study or for at least 3 or 5 months (for monotherapy and combination therapy participants, respectively) after the last dose of study drug.
研究组 & 干预措施
Arm 1
ABBV-428 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle).
干预措施: ABBV-428 (Drug)
Arm A, B, and C
Additional participants (with ovarian cancer, NSCLC, etc.) will be enrolled in a dose expansion cohorts that will further evaluate ABBV-428.
干预措施: ABBV-428 (Drug)
Arm D
Additional participants with NSCLC will be enrolled in an expansion cohort that will further evaluate ABBV-428 plus nivolumab.
干预措施: ABBV-428 (Drug)
Arm D
Additional participants with NSCLC will be enrolled in an expansion cohort that will further evaluate ABBV-428 plus nivolumab.
干预措施: Nivolumab (Drug)
Arm 2
ABBV-428 plus nivolumab.
干预措施: ABBV-428 (Drug)
Arm 2
ABBV-428 plus nivolumab.
干预措施: Nivolumab (Drug)
结局指标
主要结局
Number of participants with adverse events
时间窗: First dose of study drug through at least 100 days after end of treatment; up to 2 years after last participants first dose
Recommended Phase 2 Dose (RPTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab
时间窗: 1 day of study drug administration within the 28-day cycle at the designated cohort dose
If a maximum tolerated dose (MTD) is reached, the RPTD of ABBV-428 will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and pharmacokinetic data.
Area under the serum concentration-time curve (AUC) of ABBV-428
时间窗: Up to 30 days after a 24-month treatment period
Terminal half-life (t1/2) of ABBV-428
时间窗: Up to 30 days after a 24-month treatment period
Maximum observed serum concentration (Cmax) of ABBV-428
时间窗: Up to 30 days after a 24-month treatment period
Maximum tolerated dose (MTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab
时间窗: Up to 2 years
The highest dose level at which less than 2 of 6 participants or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.
Time to Cmax (Tmax) of ABBV-428
时间窗: Up to 30 days after a 24-month treatment period
次要结局
- Duration of Objective Response (DOR)(Up to 30 days after a 24-month of treatment period)
- Clinical benefit rate (CBR)(Up to 30 days after a 24-month of treatment period)
- Progression-Free Survival (PFS)(Up to 30 days after a 24-month of treatment period)
- Objective Response Rate (ORR)(Up to 30 days after a 24-month of treatment period)