A Phase 1 Study Evaluating the Safety, Pharmacokinetics and Anti-Tumor Activity of ABBV-176 in Subjects With Advanced Solid Tumors Likely to Express Prolactin Receptor (PRLR)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 19
- 试验地点
- 11
- 主要终点
- Dose Escalation Cohort: AUC∞ for ABBV-176
研究概览
简要总结
This is an open-label, Phase I, dose-escalation study to determine the maximum tolerated dose (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary efficacy, and pharmacokinetic (PK) profile of ABBV-176 for participants with advanced solid tumors likely to express Prolactin Receptor (PRLR). The study will consist of 2 cohorts: Dose Escalation and Expanded Recommended Phase 2 Dose.
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
- •Participant has histological confirmation of a locally advanced or metastatic solid tumor of a type associated with Prolactin Receptor (PRLR) expression that has progressed on prior treatment, is not amenable to treatment with curative intent, and has no other therapy options known to provide clinical benefit or the subject is ineligible for such therapies.
- •Dose Escalation Cohort: must have breast cancer, colorectal cancer, adrenocortical carcinoma, chromophobe renal cell carcinoma.
- •Expanded Cohort: must have breast cancer.
- •Participant must consent to provide the following for biomarker analyses:
- •Dose Escalation Cohort: archived tumor tissue or fresh tumor biopsy.
- •Expanded Cohort: archived tumor tissue and fresh tumor biopsy.
- •Participant has Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Participant has adequate bone marrow, renal, and hepatic function.
排除标准
- •Participant received anticancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic, or any investigational therapy within 21 days before Study Day 1; participant received palliative radiotherapy or small molecule targeted anti-cancer agents within 14 days of Study Day
- •Participant has prior exposure to any pyrrolobenzodiazopine-containing agent
- •Participant has unresolved, clinically significant toxicities from prior anticancer therapy, defined as greater than Grade 1 on Common Terminology for adverse events.
- •Participant has clinically significant uncontrolled conditions.
- •Participant has a history of major immunologic reaction to any Immunoglobulin G (IgG).
- •Participant has received more than 4 prior lines of systemic cytotoxic therapy (not including neo-adjuvant or adjuvant therapy).
- •For prior cytotoxic therapy, treatment for 1 full cycle or less will not be considered as prior therapy unless the patient experienced progression of disease while on that therapy.
- •Participant has a history of >= grade 3 AST, ALT, or bilirubin increase or has extensive liver resection (i.e., left lobe resection).
- •Participant has a history of cholecystitis (subject with history of cholecystectomy will not be excluded), or has active gallbladder disease.
研究组 & 干预措施
Dose Escalation Cohort
ABBV-176 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached.
干预措施: ABBV-176 (Drug)
Expanded RPTD Cohort
ABBV-176 via intravenous administration in participants with breast cancer at the Recommended Phase Two Dose (RPTD) determined during the Dose Escalation Cohort
干预措施: ABBV-176 (Drug)
结局指标
主要结局
Dose Escalation Cohort: AUC∞ for ABBV-176
时间窗: Up to approximately 57 days
AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time.
Dose Escalation Cohort: Tmax of ABBV-176
时间窗: Up to approximately 57 days
Time to Cmax (Tmax) of ABBV-176
Dose Escalation Cohort: Terminal phase elimination rate constant (β) for ABBV-176
时间窗: Up to approximately 57 days
Terminal phase elimination rate constant (β)
Dose Escalation Cohort: Maximum tolerated dose (MTD) of ABBV-176
时间窗: Minimum first cycle of dosing (up to 21 days)
MTD will be defined as the highest dose level at which less than or equal to 33% of participants experience a dose limiting toxicity.
Expanded Recommended Phase Two Dose (RPTD) Cohort: Objective Response Rate (ORR)
时间窗: Up to approximately 2 years
ORR is defined as the proportion of participants with a response of partial response (PR) or better per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Dose Escalation Cohort: AUCt for ABBV-176
时间窗: Up to approximately 57 days
Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-176.
Dose Escalation Cohort: Recommended Phase 2 dose (RPTD) for ABBV-176
时间窗: Minimum first cycle of dosing (up to 21 days)
The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Cohort.
Dose Escalation Cohort: Cmax of ABBV-176
时间窗: Up to approximately 57 days
Maximum observed plasma concentration (Cmax) of ABBV-176.
Dose Escalation Cohort: t1/2 for ABBV-176
时间窗: Up to approximately 57 days
Terminal elimination half-life (t1/2)
次要结局
- Expanded RPTD Cohort: Overall Survival (OS)(Up to 2 years after the last dose of study drug)
- Expanded RPTD Cohort: Terminal phase elimination rate constant (β) for ABBV-176(Up to approximately 15 days)
- Expanded RPTD Cohort: AUCt for ABBV-176(Up to approximately 15 days)
- Expanded RPTD Cohort: Tmax of ABBV-176(Up to approximately 15 days)
- Expanded RPTD Cohort: Cmax of ABBV-176(Up to approximately 15 days)
- Expanded RPTD Cohort: Duration of Response (DOR)(Up to approximately 2 years)
- Expanded Recommended Phase Two Dose (RPTD) Cohort: Progression-Free Survival (PFS)(Up to approximately 2 years)
- Expanded RPTD Cohort: Change in ECOG Performance Status(Up to approximately 2 years)
- Expanded RPTD Cohort: AUC∞ for ABBV-176(Up to approximately 15 days)
- Expanded RPTD Cohort: t1/2 for ABBV-176(Up to approximately 15 days)
- Dose Escalation Cohort: Change from Baseline in QTcF(Up to approximately 47 days)