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2021-11-10
2025-11
2025-11
81
NCT05057013
Cancer Research UK
Cancer Research UK
INTERVENTIONAL
A Phase I/IIa Trial of HMBD-001 in Advanced HER3 Positive Solid Tumours
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.
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. The main aims of the clinical trial are to find out: * The best dose of HMBD-001 alone and in combination with other anti-cancer drugs that should be given to participants. * More about the potential side effects of HMBD-001 when given alone and in combination with other anti-cancer agents, and how they can be managed. * What happens to HMBD-001 inside the body and how it affects cancer cells. * The potential anti-tumour activity of HMBD-001 as a single agent and in combination with other anti-cancer agents in specific tumour types of HER3-expressing tumours or tumours with NRG1 gene fusions.
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2021-09-10 | N/A | 2025-08-06 |
2021-09-24 | N/A | 2025-08-11 |
2021-09-27 | N/A | 2025-08 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Non Randomized
Interventional Model:
Parallel
Masking:
None
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| EXPERIMENTAL: HMBD-001 (Part A) | DRUG: HMBD-001
|
| EXPERIMENTAL: HMBD-001 and enzalutamide (Part B Arm 1) | DRUG: HMBD-001 and enzalutamide
|
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced Dose Limiting Toxicities (DLTs); Part A | 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. | From first dose onwards until completion of Cycle 1 (28 days) |
| Number of Participants Who Experienced DLTs; Part B Arm 1 | DLTs graded for severity using the NCI CTCAE v5.0, measured by count of participants per arm. | From first dose of combination therapy onwards until completion of Cycle 1 (28 days) |
| Number of adverse events (AEs) by arm considered to be at least possibly related to HMBD-001 (Part A and Part B Arm 1) | Number of AEs related to HMBD-001 given as a single agent and in combination with enzlutamide, graded according to NCI CTCAE v5.0. | From the date of written informed consent until the end of the safety follow-up period (maximum [max] 42 weeks per participant) |
| 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) | 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. | From the date of written informed consent until the end of the safety follow-up period (max 42 weeks per participant) |
| Overall response rate (ORR) within 6 cycles of HMBD-001 (Part B Arm 1) | 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. | From baseline radiological disease assessment until 28 days after last dose of HMBD-001 (max 36 weeks per participant) |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| ORR within 6 cycles of HMBD-001 (Part A) | Proportion of participants who achieve a best response of CR or PR, based on RECIST v1.1 and/or PCWG3 Criteria as applicable, within 6 cycles of HMBD-001 monotherapy. | 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) | Cmax of HMBD-001 in serum, analysed via enzyme linked immunosorbent assay (ELISA). Not all participants will be analysed at all timepoints. | 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) | Cmin of HMBD-001 in serum, analysed via ELISA. Not all participants will be analysed at all timepoints. | 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) | AUC of HMBD-001, analysed via ELISA. Not all participants will be analysed at all timepoint | 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) | t½ of HMBD-001 in serum, analysed via ELISA. Not all participants will be analysed at all timepoints. | 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) | Volume of distribution of HMBD-001 in serum at steady state, analysed via ELISA. Not all participants will be analysed at all timepoints. | 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) | Total body clearance of HMBD-001 measured in serum, analysed via ELISA. Not all participants will be analysed at all timepoints. | 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) | Proportion of participants achieving a best response of CR, or PR according to RECIST v1.1 and/or PCWG3 Criteria as applicable, within 8 and 16 weeks of commencing HMBD-001 as monotherapy and in combination with enzalutamide. | 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) | Proportion of participants achieving a best response of CR, PR or stable disease (SD), based on RECIST v1.1 and/or PCWG3 Criteria as applicable, within 6 cycles of HMBD-001 as monotherapy and in combination with enzalutamide. | 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) | The median duration in days from the first observation of a CR or PR, according to RECIST v1.1 and/or PCWG3 Criteria as applicable, until either progressive disease (PD) or death from any cause, in participants with a confirmed CR or PR. | 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) | The median duration in days from the first administration of HMBD-001 until either PD or death from any cause, in participants who achieve a CR, PR, or SD for at least 24 weeks, according to RECIST v1.1 and/or PCWG3 Criteria as applicable. | 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) | The median duration in days from first dose of HMBD-001 to death from any cause or PD according to RECIST v1.1 and/or PCWG3 Criteria as applicable. | 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) | The median time from first dose of HMBD-001 to death from any cause. | 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) |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
16 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
