A Phase I, Multicenter, Open-label, First-in-Human, Dose Escalation and Expansion Study of AZD9592 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 190
- 试验地点
- 48
- 主要终点
- Incidence of Adverse Events (AEs)
研究概览
简要总结
This is a first-in-human (FIH) Phase I, multi-center, open-label, study of AZD9592, in patients with advanced solid tumors. The study consists of several study modules, each evaluating the safety, tolerability, preliminary efficacy, pharmacokinetics (PK), pharmacodynamics, anti-tumor activity, and immunogenicity of AZD9592, as monotherapy or in combination with anti-cancer agents.
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
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1
- •Life expectancy ≥ 12 weeks
- •Measurable disease per RECIST v1.1
- •Adequate organ and marrow function as defined in the protocol
- •Additional Inclusion Criteria for Module 1:
- •Histologically or cytologically confirmed metastatic or locally advanced EGFRmut., NSCLC; metastatic EGFRwt. NSCLC; recurrent or metastatic HNSCC of the oral cavity; metastatic CRC.
- •Additional Inclusion Criteria for Module 2:
- •Histologically or cytologically confirmed metastatic NSCLC EGFRmut.
- •Additional Inclusion Criteria for Module 3:
- •Histologically or cytologically confirmed metastatic CRC.
排除标准
- •History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Spinal cord compression or a history of leptomeningeal carcinomatosis.
- •Active infection including tuberculosis and HBV, HCV or HIV
- •Brain metastases unless treated (prior treatment required only for Module 1), asymptomatic, stable, and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 2 weeks prior to start of study treatment.
- •Participants with cardiac comorbidities as defined in the study protocol
研究组 & 干预措施
Module 1 AZD9592 Monotherapy
Module 1 has two parts:
Part A aims to determine the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AZD9592.
Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 as monotherapy in select solid tumors
干预措施: AZD9592 (Drug)
Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin
Module 3 has two parts:
Part A aims to determine the safety, tolerability and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC) Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC)
干预措施: 5-Fluorouracil (5-FU) (Drug)
Module 2 AZD9592 Combination with Osimertinib
Module 2 has two parts:
Part A aims to determine the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with Osimertinib.
Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with Osimertinib in NSCLC EGFRm
干预措施: AZD9592 (Drug)
Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin
Module 3 has two parts:
Part A aims to determine the safety, tolerability and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC) Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC)
干预措施: AZD9592 (Drug)
Module 2 AZD9592 Combination with Osimertinib
Module 2 has two parts:
Part A aims to determine the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with Osimertinib.
Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with Osimertinib in NSCLC EGFRm
干预措施: Osimertinib (Drug)
Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin
Module 3 has two parts:
Part A aims to determine the safety, tolerability and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC) Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC)
干预措施: Leucovorin (Drug)
Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin
Module 3 has two parts:
Part A aims to determine the safety, tolerability and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC) Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC)
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Incidence of Adverse Events (AEs)
时间窗: From time of Informed Consent to 30 days post last dose of AZD9592
Number of patients with adverse events by system organ class and preferred term
Incidence of dose-limiting toxicities (DLT) as defined in the protocol
时间窗: From time of first dose of AZD9592 to end of DLT period (approximately 21 days)
Number of patients with at least 1 dose-limiting toxicity (DLT), which is any toxicity defined as a DLT in the Clinical Study Protocol
Proportion of patients with radiological response (ORR)
时间窗: From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)
Assessed by overall response rate (ORR) defined as the proportion of patients who have a confirmed complete or partial radiological response by the Investigator according to RECIST v1.1 (for patients in the dose expansion cohorts, only)
Incidence of Serious Adverse Events (SAEs)
时间窗: From time of Informed Consent to 30 days post last dose of AZD9592
Number of patients with serious adverse events by system organ class and preferred term
Incidence of baseline laboratory finding, ECG and vital signs changes
时间窗: From time of Informed Consent to 30 days post last dose of AZD9592
measured by laboratory and vital sign variables over time including change from baseline
次要结局
- Duration of Response (DoR)(From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years))
- Pharmacokinetics of AZD9592: Plasma PK concentrations(From date of first dose of AZD9592 up until 30 days post last dose)
- Pharmacokinetics of AZD9592: Maximum plasma concentration of the study drug (C-max)(From date of first dose of AZD9592 up until 30 days post last dose)
- Pharmacokinetics of AZD9592: Half-life(From date of first dose of AZD9592 up until 30 days post last dose)
- Objective Response Rate (ORR)(From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years))
- Pharmacokinetics of AZD9592: Time to maximum plasma concentration of the study drug (T-max)(From date of first dose of AZD9592 up until 30 days post last dose)
- Immunogenicity of AZD9592: Anti-Drug Antibodies (ADA)(From date of first dose of AZD9592 up until 30 days post last dose)
- Progression free Survival (PFS)(From date of first dose of AZD9592 up until date of progression or death due to any cause (approximately 2 years))
- Overall Survival (OS)(From date of first dose of AZD9592 up until the date of death due to any cause (approximately 2 years))
- Pharmacokinetics of AZD9592: Area under the concentration time curve (AUC)(From date of first dose of AZD9592 up until 30 days post last dose)
- Pharmacokinetics of AZD9592: Clearance(From date of first dose of AZD9592 up until 30 days post last dose)
- Disease Control Rate (DCR) at 12 weeks(From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (for each patient this is expected to be measured at 12 weeks))