Phase 1/2, Multicenter, Open-label, Multiple-Dose First-in-human Study of U3-1402, in Subjects With HER3 Positive Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 182
- 试验地点
- 26
- 主要终点
- Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This is an open-label, three-part, multiple-dose study to evaluate safety, tolerability, and efficacy of U3-1402 in patients with HER3-positive metastatic breast cancer. HER3 is a unique member of the human epidermal growth factor receptor, which defines a certain type of cancer.
The number of patients and treatment cycles are not fixed in this study. Subjects who continue to derive clinical benefit from the study treatment in the absence of withdrawal of consent, progressive disease (PD), unacceptable toxicity, or death may continue the study treatment until the end of the trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Is 18 Years and older in the United States or 20 Years and older in Japan
- •Has a pathologically documented advanced/unresectable or metastatic breast cancer
- •Documented HER3-positive disease measured by immunohistochemistry (IHC)
- •Has disease that is refractory to or intolerable with standard treatment, or for which standard treatment no longer is available
- •Has an Eastern Cooperative Oncology Group Performance Status 0-1
- •Has Left Ventricular Ejection Fraction ≥ 50%
- •Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- •Additional Inclusion Criteria for Dose Finding Part and Dose Expansion Part:
- •Has received 2-6 prior chemotherapy regimens for breast cancer, at least 2 of which were administered for treatment of advanced/unresectable or metastatic disease. At least 1 prior chemotherapeutic regimen must have included a taxane, administered in the neoadjuvant, adjuvant, or advanced setting. (With exception of Dose Expansion Part TNBC cohort. See additional inclusion criteria for Dose Expansion Part TNBC cohort.)
- •Additional Inclusion Criteria for Dose Expansion Part Only:
- •Is able to submit a fresh tumor biopsy sample prior to starting study treatment if not already submitted for HER3 expression
- •Has documented hormone (estrogen and/or progesterone) receptor (HR)-positive and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines. (With exception of Dose Expansion Part TNBC cohort. See additional inclusion criteria for Dose Expansion Part TNBC cohort.)
- •Additional Inclusion Criteria for Dose Expansion Part TNBC cohort Only:
- •Has documented hormone (estrogen and progesterone) receptor (HR)-negative and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines
- •Has progressed after receiving 1 to 2 prior chemotherapy regimens for advanced/unresectable or metastatic breast cancer.
排除标准
- •Prior treatment with a HER3 antibody
- •Prior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201)
- •Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or serious cardiac arrhythmia requiring treatment
- •Has a medical history of myocardial infarction or unstable angina
- •Has a corrected QT prolongation to > 450 millisecond (ms) in males and > 470 ms in females
- •Has a medical history of clinically significant lung diseases (eg, interstitial pneumonia, pneumonitis, pulmonary fibrosis, and radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period
- •Has clinically significant corneal disease
- •Additional Exclusion Criteria for Dose Expansion Part:
- •Prior treatment with an govitecan derivative (eg, IMMU-132).
研究组 & 干预措施
Dose Escalation Part
Participants receive U3-1402 from 1.6 mg/kg to 8.0 mg/kg, administered via intravenous (IV) solution at 3-week intervals.
干预措施: Patritumab Deruxtecan (Drug)
Dose Finding Part
Participants receive 1 of 5 different U3-1402 dosing regimens, administered via IV solution at 2 or 3-week intervals at doses at or lower than those studied in the Dose Escalation Part.
干预措施: Patritumab Deruxtecan (Drug)
Dose Expansion Part
Participants with HER3 high, HER2 negative, HR positive status receive 4.8 mg/kg or 6.4 mg/kg of U3-1402 administered via intravenous (IV) solution at 3-week intervals. Participants with HER3 low, HER2 negative, HR positive status receive 6.4 mg/kg of U3-1402 administered via intravenous (IV) solution at 3-week intervals. Participants with HER3 high, HER2 negative, HR negative status receive 6.4 mg/kg of U3-1402 administration via intravenous (IV) solution at 3-week intervals.
干预措施: Patritumab Deruxtecan (Drug)
结局指标
主要结局
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
时间窗: Baseline up to 28 days post last dose, up to approximately 9 months
AEs will be collected systematically from signing of the informed consent form (ICF) through 28 days after last dose
Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
时间窗: From screening until disease progresses, up to approximately 9 months
CR was defined as a disappearance of all target and non-target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target and non-target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target and non-target lesions. Objective response rate is the number of patients with confirmed complete response and confirmed partial response.
次要结局
- Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))
- Dose Finding Part: AUC of Anti-HER3-ac-DXd(Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days))
- Dose Expansion Part: AUC of Anti-HER3-ac-DXd(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))
- Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))
- Dose Finding Part: Cmax of Anti-HER3-ac-DXd(Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days))
- Dose Expansion Part: Cmax of Anti-HER3-ac-DXd(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))
- Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))
- Dose Finding Part: Tmax of Anti-HER3-ac-DXd(Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days))
- Dose Expansion Part: Tmax of Anti-HER3-ac-DXd(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))
- Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))
- Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody(Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days))
- Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))
- Dose Escalation Part: Cmax of Total Anti-HER3 Antibody(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))
- Dose Finding Part: Cmax of Anti-HER3 Antibody(Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days))
- Dose Expansion Part: Cmax in Anti-HER3 Antibody(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))
- Dose Escalation Part: Tmax of Total Anti-HER3 Antibody(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))
- Dose Finding Part: Tmax of Anti-HER3 Antibody(Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days))
- Dose Expansion Part: Tmax in Anti-HER3 Antibody(Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days))