A Phase I Open-label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Activity of AUBE00 in Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 5
- 主要终点
- Adverse events of AUBE00 [Part A, B, C]
研究概览
简要总结
This is a first-in-human, Phase I, open-label, multicenter, multinational study, designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and anti-tumor activity of AUBE00 in patients with locally advanced or metastatic solid tumors.The total number of patients in this study will be approximately 90 to 130.
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
- •Age ≥ 18 years at time of signing Informed Consent Form (ICF)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Patients with Kirsten rat sarcoma (KRAS) alteration confirmed by local tests or central laboratory test (Details are defined for each part)
- •Refractory or resistant to standard therapies or standard therapies are not available
排除标准
- •Pregnant or breastfeeding, or intending to become pregnant or breastfeeding during the study or within 27 weeks after the last dose of AUBE00 or within 2 months after the last dose of cetuximab, whichever is longer.
- •Primary central nervous system (CNS) malignancy, untreated CNS metastases requiring any anti-tumor treatment, or active CNS metastases (progressing or requiring corticosteroids for symptomatic control)
- •Significant cardiovascular disease, such as New York Heart Association (NYHA) Class II or greater cardiac disease, unstable angina, or myocardial infraction within the previous 6 months or unstable arrhythmias within the previous 3 months
- •Patient with complications from a cerebrovascular disorder (such as subarachnoid hemorrhage, cerebral infarction, transient ischemic attack, etc.) or a history of such complications within 6 months prior to enrollment
研究组 & 干预措施
Part B: Expansion part of AUBE00 monotherapy
Patients will receive AUBE00 as an oral administration at multiple dose levels determined to be safe (including MTD).
干预措施: AUBE00 (Drug)
Part C: Dose-Escalation and Expansion part of AUBE00 in combination with Cetuximab
Patients will receive AUBE00 as an oral administration in combination with cetuximab as an IV infusion at escalated doses or the recommended dose level.
干预措施: AUBE00 (Drug)
Part A: Dose Escalation part of AUBE00 monotherapy with or without prophylactic management
Patients will receive AUBE00 as an oral administration at escalated doses. Patients may also receive prophylactic management for treatment-related adverse events.
干预措施: AUBE00 (Drug)
Part C: Dose-Escalation and Expansion part of AUBE00 in combination with Cetuximab
Patients will receive AUBE00 as an oral administration in combination with cetuximab as an IV infusion at escalated doses or the recommended dose level.
干预措施: Cetuximab (Drug)
结局指标
主要结局
Adverse events of AUBE00 [Part A, B, C]
时间窗: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)
Incidence, nature, and severity of adverse events (AEs), with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0)
Number of participants with changes in vital signs of AUBE00 [Part A, B, C]
时间窗: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)
Change from baseline in vital signs (Includes respiratory rate, pulse oximetry, pulse rate, and systolic and diastolic blood pressure while the patient is in a seated or semi-recumbent position, and temperature.)
Number of participants with changes in clinical laboratory test of AUBE00 [Part A, B, C]
时间窗: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)
Change from baseline in clinical laboratory test
Number of participants with changes in Electrocardiograms (ECGs) of AUBE00 [Part A, B, C]
时间窗: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)
Change from baseline in ECGs (QT interval)
Maximum tolerated dose (MTD) of AUBE00 [Part A, C]
时间窗: From Cycle 0 Day 1 until Cycle 2 Day 1 (approximately 30 days) (Cycle 0: 6 to 9 days, Cycle 1 and beyond each Cycle: 21 days) [Part A]; From Cycle 1 Day 1 until Cycle 2 Day 1 (approximately 28 days) (Cycle 1 and beyond each Cycle: 28 days) [Part C]
Incidence and nature of dose-limiting toxicities (DLTs)
Time to reach maximum plasma concentration (Tmax) of AUBE00 [Part A]
时间窗: From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)
Tmax of AUBE00
Maximum plasma concentration (Cmax) of AUBE00 [Part A]
时间窗: From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)
Cmax of AUBE00
Elimination half-life (t1/2) of AUBE00 [Part A]
时间窗: From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)
t1/2 of AUBE00
Area under the plasma concentration-time curve (AUC) of AUBE00 [Part A]
时间窗: From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)
AUC of AUBE00
Objective response of AUBE00 [Part B, C]
时间窗: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)
Objective response, defined as a confirmed complete response (CR) or partial response (PR) as the best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by the Investigator
次要结局
- Objective response of AUBE00 [Part A](From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months))
- Disease control of AUBE00 [Part A, B, C](From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months))
- Duration of response (DoR) of AUBE00 [Part A, B, C](From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months))
- Progression free survival (PFS) of AUBE00 [Part A, B, C](From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months))
- Anti-AUBE00 antibodies of AUBE00 [Part A, B, C](From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months))
- Overall survival (OS) of AUBE00 [Part B, C](From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months))
- Time to reach maximum plasma concentration (Tmax) of AUBE00 [Part B, C](From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part B]. From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C].)
- Maximum plasma concentration (Cmax) of AUBE00 [Part B, C](From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part B]. From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C].)
- Elimination half-life (t1/2) of AUBE00 [Part B, C](From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)[Part B]. From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C].)
- Area under the plasma concentration-time curve (AUC) of AUBE00 [Part B, C](From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)[Part B]. From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C].)
- Time to reach maximum serum concentration (Tmax) of cetuximab [Part C](From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C].)
- Maximum serum concentration (Cmax) of cetuximab [Part C](From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C].)
- Elimination half-life (t1/2) of cetuximab [Part C](From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C].)
- Area under the serum concentration-time curve (AUC) of cetuximab [Part C](From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C].)
- Anti-cetuximab antibodies of cetuximab [Part C](From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C].)