A Phase 1 Open-Label, Dose Escalation and Expansion Trial to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of CB307, a Trispecific Humabody® T-cell Enhancer, in Patients With PSMA+ Advanced and/or Metastatic Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 19
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
研究概览
简要总结
FIH, Phase 1, open-label, multi centre study of CB307, a trispecific Humabody® T-cell enhancer, in patients with advanced and/or metastatic PSMA+ solid tumours to assess safety and tolerability to determine MTD and preliminary RP2D.In addition this study will assess the safety and efficacy of CB307 when given in combination with pembrolizumab (KEYTRUDA®) in patients with metastatic PSMA+ castration-resistant cancer
详细描述
FIH, Phase 1, open-label, multi centre, non randomised study of CB307, a trispecific Humabody® T-cell enhancer, in patients with advanced and/or metastatic PSMA+ solid tumours (Part 1 & 2A) and patients with metastatic PSMA+ castration-resistant cancer (Part 2B) . The study will consist of a dose escalation phase (Part 1) and a cohort expansion phase (Part 2) which will consist of 2 arms . Part 2 will evaluate safety and preliminary efficacy of CB307 (both as monotherapy and in combination with pembrolizumab) at the MTD or preliminary RP2D as determined in Part 1. Approximately 70 patients will participate in total. Patients will receive either CB307 alone or CB307 with pembrolizumab IV (Part 2B), until loss of clinical benefit, unacceptable toxicity, withdrawal of consent or end of study. The dose escalation may be adapted by the SRC based on clinical experience and safety review.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label multi center non randomised study.
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
- •Capable of understanding the written informed consent
- •Aged at least 18 years
- •Not amenable to standard of care
- •ECOG PS <=2
- •Has documented histologically confirmed diagnosis of PSMA+ advanced or metastatic solid tumours
- •Has radiologically measurable disease per RECIST v1.1 or elevated serum PSA for castration resistant prostate cancer patients with only bone metastasis
- •Adequate organ function
排除标准
- •Subjects with autoimmune disease or regular immunosuppressants
- •Has discontinued from anti-CTLA 4, anti-PD1 or anti-PD(L)1 antibody because of intolerable toxicity
- •Has brain metastasis including leptomeningeal metastasis or primary brain tumour
- •Has current or history of CNS disease
- •Has known active infection
- •Part 2B only - has prior treatment with anti PD(L)1 or anti CTLA4
研究组 & 干预措施
Multi center open label Dose Escalation followed by Cohort Expansion: Part 2A
Patients will receive CB307 IV infused every 7 days. Duration of treatment cycle is 21 days. Once the Dose Escalation phase (Part 1) is completed Cohort Expansion phase (Part 2) will begin. Part 2A arm will enrol patients with PSMA+ solid tumours. Treatment will continue until loss of clinical benefit, intolerable toxicity, withdrawal of consent or the study is stopped. Estimated study duration is 20 months.
干预措施: CB307 (Drug)
Multi center open label Dose Escalation followed by Combination Cohort Expansion : Part 2B
Patients will receive CB307 IV infused every 7 days in combination with KEYTRUDA® (pembrolizumab) IV infused every 21 days . Duration of treatment cycle is 21 days. Once the Dose Escalation phase (Part 1) is completed Cohort Expansion phase (Part 2) will begin. Part 2B arm will enrol patients with PSMA+ metastatic castration-resistant prostate cancer. Treatment will continue until loss of clinical benefit, intolerable toxicity, withdrawal of consent or the study is stopped. Estimated study duration is 20 months.
干预措施: CB307 (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
时间窗: The nature and frequency of any DLTs during the DLT-monitoring period assessed based on NCI CTCAE v5.0. up to 20 months duration.
The objective of the study is to assess the safety and tolerability of the study drug CB307 and to determine the MTD (maximum tolerated dose)
Number of participants with treatment-related adverse events with CB307 in combination with pembrolizumab as assessed by CTCAE v5.0
时间窗: The nature and frequency of any DLTs during the DLT-monitoring period for participants with combination therapy, assessed based on NCI CTCAE v5.0. up to 20 months duration.
The objective of the study is to assess the safety and tolerability of the study drug CB307 in combination with pembrolizumab to assess safety and tolerability of the combined treatment regimen
次要结局
- Pharmacokinetic of CB307 T1/2(Data collected up to 20 months duration.)
- To evaluate anti-tumor response according to RECIST v.1.1 or PCWG3(anti-tumor response according to RECIST v1.1 or PCWG3 up to 20 months duration;)
- To measure how the body processes CB307 in the body over time(PK parameters of CB307: data collected at time point 0 at each dosing period up to 20 months duration.)
- Pharmacokinetic of CB307 Tmax(Data collected up to 20 months duration.)
- To measure Tumour Immune response(Tumor response per RECIST ver 1.1 up to 20 months duration)
- Relationship of CB307 to anti tumour response(PSA response defined as a >50% decrease in PSA up to 20 months duration)
- To evaluate clinical efficacy measured as progression-free survival according to RECIST v.1.1 or PCWG3(Progression-free survival according to RECIST v1.1 or PCWG3 up to 20 months duration; and change from baseline in anti-drug (CB307) antibodies (ADA up to 20 months duration)
- To evaluate clinical efficacy and duration of response by radiographic progression free survival (rPFS)(radiographic progression free survival up to 20 months duration;)