A Cancer Research UK Phase I/IIa Open Label, Dose Escalation and Expansion Trial of HMBD-001 (an Anti-HER3 Monoclonal Antibody) Given Intravenously as a Single Agent and in Combination in Patients With Advanced HER3 Positive Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 81
- 试验地点
- 4
- 主要终点
- Number of Participants Who Experienced Dose Limiting Toxicities (DLTs); Part A
研究概览
简要总结
This clinical trial is evaluating a drug called HMBD-001 (an anti-HER3 monoclonal antibody) in participants with advanced HER3 positive solid tumours. The main aims are to find out the best dose of HMBD-001 that can be given to participants alone and in combination with other anti-cancer agents, more about the potential side effects of HMBD-001 and how they can be treated, and what happens to HMBD-001 inside the body and how it affects cancer cells.
详细描述
HMBD-001 is a type of drug called a monoclonal antibody. It works by targeting a protein called HER3, which is found in high numbers in some types of cancers including those that contain fusions in a gene called NRG1. By attaching itself to this protein, it may then work to kill the cancer cells or to stop them growing.
This is a first-in-human clinical trial that has two parts:
Part A is a 'dose escalation' phase where small groups of participants will receive increasing doses of HMBD-001 on its own (as a single agent) to find the safest dose that best targets cancer cells.
Part B is a 'dose expansion' phase where larger groups of participants with specific cancer types that are known to have high levels of the protein HER3 or that have a confirmed NRG1 gene fusion will receive the highest doses of HMBD-001 considered to be safe as monotherapy from Part A in combination with other anti-cancer drugs that are already licensed for use.
In Part B Arm 1, participants will receive HMBD-001 in combination with enzalutamide. Enzalutamide is a drug used to treat prostate cancer. Prostate cancer is known to be sensitive to androgens (hormones associated with male characteristics), and enzalutamide blocks the action of androgens by limiting the binding of androgens to androgen receptors. This slows the growth of prostate cancer cells and may kill them.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
HMBD-001 (Part A)
干预措施: HMBD-001 (Drug)
HMBD-001 and enzalutamide (Part B Arm 1)
干预措施: HMBD-001 and enzalutamide (Drug)
结局指标
主要结局
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs); Part A
时间窗: From first dose onwards until completion of Cycle 1 (28 days)
DLTs graded for severity using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0, measured by count of participants per arm.
Number of Participants Who Experienced DLTs; Part B Arm 1
时间窗: From first dose of combination therapy onwards until completion of Cycle 1 (28 days)
DLTs graded for severity using the NCI CTCAE v5.0, measured by count of participants per arm.
Number of adverse events (AEs) by arm considered to be at least possibly related to HMBD-001 (Part A and Part B Arm 1)
时间窗: From the date of written informed consent until the end of the safety follow-up period (maximum [max] 42 weeks per participant)
Number of AEs related to HMBD-001 given as a single agent and in combination with enzlutamide, graded according to NCI CTCAE v5.0.
Number of Grade 3, 4 and 5 AEs by arm considered to be at least possibly related to HMBD-001 (Part A and Part B Arm 1)
时间窗: From the date of written informed consent until the end of the safety follow-up period (max 42 weeks per participant)
Number of Grade 3, 4 and 5 AEs related to HMBD-001 given as a single agent and in combination with enzalutamide, graded according to NCI CTCAE v5.0.
Overall response rate (ORR) within 6 cycles of HMBD-001 (Part B Arm 1)
时间窗: From baseline radiological disease assessment until 28 days after last dose of HMBD-001 (max 36 weeks per participant)
Proportion of participants who achieve a best response of complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 and/or Prostate Cancer Working Group 3 (PCWG3) Criteria as applicable, within 6 cycles of HMBD-001 in combination with enzalutamide.
次要结局
- ORR within 6 cycles of HMBD-001 (Part A)(From baseline radiological disease assessment until 28 days after last dose of HMBD-001 (max 32 weeks per participant))
- Maximum observed serum concentration (Cmax) of HMBD-001 (Part A and Part B Arm 1)(Up to 31 timepoints from first dose until 28 days after the last dose of HMBD-001 (max 28 weeks per participant))
- Minimum observed serum concentration (Cmin) of HMBD-001 (Part A and Part B Arm 1)(Up to 31 timepoints from first dose until 28 days after the last dose of HMBD-001 (max 28 weeks per participant))
- Area under the serum concentration-time curve (AUC) of HMBD-001 (Part A and Part B Arm 1)(Up to 31 timepoints from first dose until 28 days after the last dose of HMBD-001 (max 28 weeks per participant))
- Terminal elimination half-life (t½) of HMBD-001 (Part A and Part B Arm 1)(Up to 31 timepoints from first dose until 28 days after the last dose of HMBD-001 (max 28 weeks per participant))
- Steady state volume of distribution of HMBD-001 in serum (Part A and Part B Arm 1)(Up to 31 timepoints from first dose until 28 days after the last dose of HMBD-001 (max 28 weeks per participant))
- Total body clearance of HMBD-001 (Part A and Part B Arm 1)(Up to 31 timepoints from first dose until 28 days after the last dose of HMBD-001 (max 28 weeks per participant))
- ORR within 8 and 16 weeks of commencing HMBD-001 (Part A and Part B Arm 1)(From baseline radiological disease assessment up to 16 weeks post first HMBD-001 administration (max 24 weeks per participant))
- Disease control rate within 6 cycles of HMBD-001 (Part A and Part B Arm 1)(From baseline radiological disease assessment up to 28 days post last HMBD-001 administration (max 36 weeks per participant))
- Duration of response (Part A and Part B Arm 1)(From the date of first recorded response until 24 months after the last enrolled participant's first dose of HMBD-001 (max 48 months per participant))
- Duration of clinical benefit (Part A and Part B Arm 1)(From the date of first recorded response until 24 months after the last enrolled participant's first dose of HMBD-001(max 48 months per participant))
- Progression free survival (Part B Arm 1)(From first dose of HMBD-001 until 24 months after the last enrolled participant's first dose of HMBD-001 (max 48 months per participant))
- Overall survival (Part B Arm 1)(From first dose of HMBD-001 until 24 months after the last enrolled participant's first dose of HMBD-001 (max 48 months per participant))