A Phase 1/2 Study to Investigate the Safety, Pharmacokinetics, and Efficacy of CRB-701, an Antibody-drug Conjugate Targeting Nectin-4, in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 348
- 试验地点
- 81
- 主要终点
- Part A: To confirm the safety and tolerability and determine MTD and PADR for CRB-701
研究概览
简要总结
The goal of this clinical trial is to define a safe and effective dose of CRB-701 for participants with solid tumors that are expressing a protein called nectin-4.
The main questions it aims to answer are:
What is the the safe and effective dose of CRB-701? What cancers can be treated effectively with CRB-701?
Participants will be asked to attend clinic and be given a intravenous infusion of CRB-701. They will have blood tests, CT or MRI Scans, and other assessments to measure whether CRB-701 has an effect on tumors.
详细描述
This is a three-part open-label, Phase 1/2 clinical trial designed to evaluate the safety, PK, and efficacy of CRB-701 in participants with advanced solid tumors expressing nectin-4.
Part A will include solid tumor types known to express nectin-4. Dose escalation will be guided by the Bayesian optimal interval (BOIN) design to determine the Maximum Tolerated Dose (MTD) of CRB-701. Four (4) dose groups are pre-determined. Dose escalation/de-escalation decisions are made based on the occurrence of DLT.
Part B will evaluate two dose levels of CRB-701 alone and in combination with anti-PD-1 by using a time-to-event Bayesian optimal Phase 2 study design to optimize the dose of CRB-701 in one or more separate cohorts of participants with nectin-4-positive tumors.
During Part C, the recommended dose level of CRB-701 for further exploration defined in Part B will explore CRB-701 alone or combined with anti-PD-1 in up to seven separate cohorts of participants with advanced tumors known to express Nectin-4.
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
- •Confirmed diagnosis of select advanced or metastatic nectin-4 expressing solid tumors that have progressed having exhausted all appropriate lines of therapy or have no other standard therapy with proven clinical benefit. In Part C, HNSCC participants may enroll as first-line therapy.
排除标准
- •Active of uncontrolled CNS metastases
- •History of solid tumors other than the diseases under study
- •History of and/or current cardiovascular events or conditions in the previous 6 months
- •Pre-existing >/= Grade 2 neuropathy
- •Hemoglobin A1C (HbA1C) >/= 8%, uncontrolled diabetes mellitus or know diabetic neuropathy
- •Active ocular disease at baseline
- •Chronic severe liver disease or live cirrhosis
- •Interstitial lung disease or pneumonitis within 6 months on initiating treatment on study
- •Other significant cormorbidities.
研究组 & 干预措施
Part A Dose Escalation - CRB-701 Dose Level 1
CRB-701 Dose level 1, intravenous infusion over 30 mins, Dose schedule 1
干预措施: CRB-701 (Drug)
Part A Dose Escalation - CRB-701 Dose Level 2
CRB-701 Dose Level 2, intravenous infusion over 30 mins, Dose schedule 1
干预措施: CRB-701 (Drug)
Part A Dose Escalation - CRB-701 Dose Level 3
CRB-701 Dose Level 3, intravenous infusion over 30 mins, dose schedule 1
干预措施: CRB-701 (Drug)
Part A Dose Escalation - CRB-701 Dose Level 4
CRB-701 Dose Level 4, intravenous infusion over 30 mins, dose schedule 1
干预措施: CRB-701 (Drug)
Part B Dose Optimization: CRB-701 High dose
Selected high dose of CRB-701, intravenous infusion over 30 mins, dose schedule 1
干预措施: CRB-701 (Drug)
Part B Dose Optimization: CRB-701 low dose
Selected Low dose of CRB-701, intravenous infusion over 30 mins
干预措施: CRB-701 (Drug)
Part C Dose Expansion - Cohort 1
Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: CRB-701 (Drug)
Part C Dose Expansion - Cohort 1
Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: Anti-PD-1 (Drug)
Part C Dose Expansion - Cohort 2
Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins
干预措施: CRB-701 (Drug)
Part C Dose Expansion - Cohort 3
Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: CRB-701 (Drug)
Part C Dose Expansion - Cohort 3
Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: Anti-PD-1 (Drug)
Part C Dose Expansion - Cohort 4
Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins
干预措施: CRB-701 (Drug)
Part C Dose Expansion - Cohort 5
Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: CRB-701 (Drug)
Part C Dose Expansion - Cohort 5
Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: Anti-PD-1 (Drug)
Part B Dose Optimization: CRB-701 high dose combined with anti-PD-1
Selected high dose of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: CRB-701 (Drug)
Part B Dose Optimization: CRB-701 high dose combined with anti-PD-1
Selected high dose of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: Anti-PD-1 (Drug)
Part B Dose Optimization: CRB-701 low dose combined with anti-PD-1
Selected low dose of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: CRB-701 (Drug)
Part B Dose Optimization: CRB-701 low dose combined with anti-PD-1
Selected low dose of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: Anti-PD-1 (Drug)
Part C Dose Expansion - Cohort 6
Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins
干预措施: CRB-701 (Drug)
Part C Dose Expansion - Cohort 7
Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: CRB-701 (Drug)
Part C Dose Expansion - Cohort 7
Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1
干预措施: Anti-PD-1 (Drug)
结局指标
主要结局
Part A: To confirm the safety and tolerability and determine MTD and PADR for CRB-701
时间窗: 21 days
Occurrence of Dose Limiting Toxicities as defined in the protocol
Part B & C: To evaluate efficacy in terms of Objective Response Rate (ORR)
时间窗: Up to 6 months
ORR is the percentage of participants that achieve a response (CR + PR) using RECIST 1.1
次要结局
- Parts A, B, & C: To characterize the safety profile of CRB-701(Up to 6 months)
- Maximum observed plasma concentration of CRB-701 [total ADC] (Cmax)(Approximately 9 weeks)
- Maximum observed plasma concentration of free MMAE (Cmax)(Approximately 9 weeks)
- Part B & C : To evaluate efficacy in terms of Disease Control Rate (DCR)(Up to 6 months)
- Maximum observed plasma concentration of Total CRB-701 antibody [Tab] (Cmax)(Approximately 9 weeks)
- Time to reach Cmax of Total CRB-701 [Total ADC] (Tmax)(Approximately 9 weeks)
- Time to reach Cmax of free MMAE (Tmax)(Approximately 9 weeks)
- Time to reach Cmax of Total CRB-701 antibody [Tab] (Tmax)(Approximately 9 weeks)
- Time to reach Cmax of Total CRB-701 antibody [Tab] (Cmax)(Approximately 9 weeks)
- Total Area Under the plasma concentration-time curve of Total CRB-701 [total ADC] (AUC)(Approximately 9 weeks)
- Total Area Under the plasma concentration-time curve of free MMAE (AUC)(Approximately 9 weeks)
- Total Area Under the plasma concentration-time curve of Total CRB-701 antibody [Tab] (AUC)(Approximately 9 weeks)