A Phase 1 First in Human, Multicenter, Open-Label Dose-Escalation Study to Determine the Safety, Tolerability, Pharmacokinetics, and RP2D of ABBV-184 in Subjects With Previously Treated Cancers
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 14
- 试验地点
- 17
- 主要终点
- Recommended Phase 2 Dose (RP2D) of ABBV-184 (Dose-Escalation Phase)
研究概览
简要总结
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. This study focuses on two types of cancers: Acute Myeloid Leukemia (AML) and Non-Small Cell Lung Cancer (NSCLC). AML (blood cancer) is cancer of the white blood cells (WBC). NSCLC (solid tumor) is a disease in which cancer cells form in the tissues of the lung. The purpose of this study is to determine recommended phase 2 dose (RP2D) and to see if the study drug is safe and able to treat patients who have AML and NSCLC.
ABBV-184 is an investigational drug being developed for treatment of cancer. The study has two arms and two phases: AML arm and NSCLC arm; dose escalation and dose expansion phase. Adult participants with diagnosis of AML or NSCLC will be enrolled. In dose escalation phase, around 36 participants will be enrolled in each arm. In dose expansion phase, around 20 participants will be enrolled in each arm. The study will be conducted in approximately 50 sites across 10 countries.
Participants will receive weight based intravenous (IV) infusion of ABBV-184 once a week. At the beginning of the study, visits will occur daily during hospitalization followed by less frequently over time.
There will be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood tests, checking for side effects, and questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Diagnosis of acute myeloid leukemia (AML) or non-small cell lung cancer (NSCLC).
- •Participants must consent to hospitalization for at least 72 hours following the first two doses of ABBV-184 in Cycle
- •Participants must have Human Leukocyte Antigen-A2 (HLA-A2) restricted genotype. Participants must be HLA-A2:01 positive in at least one allele tested with a high-resolution HLA genotyping assay performed in a College of American Pathologists (CAP)/Clinical Laboratory Improvement Act (CLIA)-certified or equivalent laboratory.
- •Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Laboratory values and cardiac function must meet the protocol specifications.
排除标准
- •For AML participants:
- •Presence or history of extramedullary disease are ineligible, participants with a diagnosis of acute promyelocytic leukemia (APL) or BCR-ABL-positive leukemia are not eligible.
- •For NSCLC participants:
- •Tumors with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) gene rearrangements are not eligible.
- •Active/uncontrolled central nervous system (CNS) leukemia/lung cancer are not eligible for the study.
- •History of inflammatory bowel disease, interstitial lung disease (pneumonitis), myocarditis, Stevens-Johnson syndrome, toxic epidermal necrolysis, solid organ transplantation, active autoimmune disease (with exceptions of vitiligo, Type I diabetes mellitus, hypothyroidism, and psoriasis), primary immunodeficiency.
- •History of clinical diagnosis of tuberculosis or major immunologic reaction to any immunoglobulin G (IgG)-containing agent are not eligible.
- •Previously received anti-cancer treatment with an agent that targets the immune system by engaging cluster of differentiation 3 (CD3) are not eligible.
研究组 & 干预措施
Dose Escalation: Participants With AML
Participants with relapsed or refractory (R/R) AML will receive escalating doses of ABBV-184
干预措施: ABBV-184 (Drug)
Dose Escalation: Participants With NSCLC
Participants with relapsed or refractory (R/R) NSCLC will receive escalating doses of ABBV-184
干预措施: ABBV-184 (Drug)
Dose Expansion: Participants With AML
Participants with R/R AML will receive ABBV-184 at recommended Phase 2 dose (RP2D) determined in dose escalation phase for AML
干预措施: ABBV-184 (Drug)
Dose Expansion: Participants With NSCLC
Participants with R/R NSCLC will receive ABBV-184 at RP2D determined in dose escalation phase for NSCLC
干预措施: ABBV-184 (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D) of ABBV-184 (Dose-Escalation Phase)
时间窗: Up to 1 Cycle after the last participant is enrolled in dose escalation phase (Approximately 2 years)
The RP2D of ABBV-184 will be determined during the dose-escalation phase of the study. RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data.
Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh) Rate (Dose Expansion Phase in Participants With AML)
时间窗: Up to 30 days after last participant complete study drug (Approximately 3 years)
CR/CRh rate is assessed based on the Clopper-Pearson (exact) method.
Objective Response Rate (ORR) (Dose Expansion Phase in Participants With NSCLC)
时间窗: Up to 30 days after last participant complete study drug (Approximately 3 years)
ORR is defined as participants with confirmed complete or partial response (CR+PR) per RECIST, v1.1
次要结局
- Number of Participants with Adverse Events (AEs)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Change in Vital Signs(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Change in Montreal Cognitive Assessment (MoCA)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Duration of Response (DOR) (Dose Expansion Phase)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Change in Laboratory Parameters(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Change in Echocardiogram(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Change in Electrocardiogram (ECG)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Maximum Observed Serum Concentration (Cmax) of ABBV-184(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Time to Maximum Observed Serum Concentration (Tmax)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Terminal Phase Elimination Rate Constant (β) for ABBV-184(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Terminal Phase Elimination Half-life (t1/2) of ABBV-184(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Area Under the Serum Concentration-Time Curve of ABBV-184(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Percentage of Participants With Anti-drug Antibodies (ADAs)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Progression-free Survival (PFS) (Dose Expansion Phase)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Relapse-Free Survival (RFS) (Dose Expansion Phase in Participants With AML)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Change in Bone Marrow Blast Count (Dose Expansion Phase in Participants With AML)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Change in Peripheral Blood Blast Count (Dose Expansion Phase in Participants With AML)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Objective Response Rate (ORR) (Dose Expansion Phase in Participants With AML)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Rate of Conversion to Transfusion Independence (Dose Expansion Phase in Participants With AML)(Up to 30 days after last participant complete study drug (Approximately 3 years))
- Clinical Benefit Rate (CBR) (Dose Expansion Phase in Participants With NSCLC)(Up to 30 days after last participant complete study drug (Approximately 3 years))