A Phase 1/2, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AVZO-103, a Nectin4/Trop2 ADC, as a Single Agent and in Combination Therapy in Patients With Locally Advanced or Metastatic Urothelial Cancer or Other Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 355
- 试验地点
- 15
- 主要终点
- Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1)
研究概览
简要总结
This study, the first clinical trial of AVZO-103, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of AVZO-103 when administered intravenously as a monotherapy and in combination therapy to patients with locally advanced or metastatic urothelial cancer or other solid tumors.
详细描述
Phase 1 is a dose escalation phase which will assess the safety and tolerability of AVZO-103 and determine the maximum tolerated dose (MTD) and preliminary recommended Phase 2 dose (RP2D) of AVZO-103 as a monotherapy. This data can guide selection of combination schedules and agents.
Phase 2 is a dose expansion phase that will aim to assess the antitumor activity of AVZO-103 as a monotherapy and in combination therapy.
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
- •Patient must be an adult, 18 years of age and older with an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 and a life expectancy of > 3 months.
- •Patients with histologically or cytologically confirmed locally advanced/metastatic malignancies for tumor types of preferred indications:
- •o Locally advanced or metastatic urothelial cancer and other solid tumors (as specified in the protocol).
- •Measurable disease as assessed by Investigator using RECIST v1.
- •Agree to provide molecular test report results to confirm eligibility and archival tumor samples and/or fresh biopsy, as applicable.
- •Other protocol-defined Inclusion criteria apply.
排除标准
- •Patients with active central nervous system (CNS) metastases are not eligible. Patients with asymptomatic and treated brain metastases may participate if they are radiologically stable for at least 4 weeks prior to the first dose of this study and do not require steroid treatment. Patients with suspected or confirmed leptomeningeal disease are not eligible, even if treated.
- •Prior Stevens-Johnson syndrome/toxic epidermal necrolysis.
- •History of drug-induced interstitial lung disease (ILD).
- •History of any serious cardiovascular condition.
- •Infection requiring IV antibiotics, antivirals, or antifungals within 2 weeks prior to first dose.
- •History of allogenic stem cell or solid organ transplant.
- •Other protocol-defined Exclusion criteria apply.
研究组 & 干预措施
Phase 2, monotherapy
Part A
干预措施: AVZO-103 (Drug)
Phase 2, combination
Part B
干预措施: AVZO-103 (Drug)
Phase 1, combination
Part B
干预措施: Combination Agent (Drug)
Phase 1, monotherapy
Part A
干预措施: AVZO-103 (Drug)
Phase 1, combination
Part B
干预措施: AVZO-103 (Drug)
Phase 2, combination
Part B
干预措施: Combination Agent (Drug)
结局指标
主要结局
Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1)
时间窗: Approximately 2 years
Number of participants with DLTs assessed for severity using CTCAE v5.0 criteria will be summarized by dose level.
Determine the maximum tolerated dose (MTD) and/or preliminary recommended Phase 2 dose (RP2D) (Phase 1)
时间窗: Approximately 16 months
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1)
时间窗: From baseline until end of study treatment or study completion (approximately 2 years)
Objective Response Rate (ORR) (Phase 2)
时间窗: From baseline through disease progression or study completion (approximately 2 years)
Defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1.
次要结局
- Objective Response Rate (ORR) (Phase 1)(From baseline through disease progression or study completion (approximately 2 years))
- Duration of Response (DOR) (Phase 1 and 2)(From baseline through disease progression or study completion (approximately 2 years))
- Disease Control Rate (DCR) (Phase 1 and 2)(From baseline through disease progression or study completion (approximately 2 years))
- Progression Free Survival (PFS) (Phase 1 and 2)(From baseline through time to event on study or study completion (approximately 2 years))
- Overall Survival (OS) (Phase 1 and 2)(Approximately 76 months)
- PK Parameters: Maximum observed concentration (Cmax) (Phase 1)(Up to 2 years)
- PK Parameters: Minimum observed concentration (Cmin) (Phase 1)(Up to 2 years)
- PK Parameters: Time to maximum observed concentration (Tmax) (Phase 1)(Up to 2 years)
- PK Parameters: Elimination half-life (T1/2) (Phase 1)(Up to 2 years)
- PK Parameters: Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) (Phase 1)(Up to 2 years)
- PK Parameters: Area under the concentration-time curve from time 0 to infinity (AUCinf) (Phase 1)(Up to 2 years)
- PK Parameters: Area under the concentration-time curve from time 0 to the end of the dosing period (AUCτ) (Phase 1)(Up to 2 years)
- Determination of RP2D (Phase 2)(Approximately 16 months)
- Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 2)(From baseline until end of study treatment or study completion (approximately 2 years))
- PK Parameters: Apparent Clearance (CL/F) (Phase 1)(Up to 2 years)
- PK Parameters: Apparent volume of distribution at steady-state (Vss) (Phase 1)(Up to 2 years)
- PK Parameters: Accumulation ratio (AR) (Phase 1)(Up to 2 years)