Trials / Active Not Recruiting

Active Not RecruitingNCT05057013

A Phase I/IIa Trial of HMBD-001 in Advanced HER3 Positive Solid Tumours

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

Status: Active Not Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 81 (estimated)

Sponsor: Cancer Research UK · Academic / Other
Sex: All
Age: 16 Years
Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

Interventions

Type	Name	Description
DRUG	HMBD-001	Participants with advanced solid tumours will receive their assigned dose level of HMBD-001 diluted in 0.9% sodium chloride, administered once a week as a 120-minute intravenous (IV) infusion. Cycles are 28 days with no break in between; administration may continue for up to 6 cycles but may continue for longer if the participant is deemed to be benefitting.
DRUG	HMBD-001 and enzalutamide	Participants with metastatic castration resistant prostate cancer (mCRPC) confirmed as HER3 positive with no PTEN loss or with a NRG1 fusion rearrangement will receive the HMBD-001 recommended Phase 2 dose (RP2D) as determined in Part A, diluted in 0.9% sodium chloride and administered once a week as a 120-minute IV infusion, in combination with enzalutamide administered at a fixed dose of 160 mg once daily, in 28-day cycles with no break between cycles. Immediately before commencing combination therapy, participants may receive one 28-day cycle of enzalutamide monotherapy to confirm that their disease does not respond to enzalutamide alone. HMBD-001 may be administered for up to 6 cycles; enzalutamide may be continued until disease progression or unacceptable toxicity.

Timeline

Start date: 2021-11-10
Primary completion: 2025-11-01
Completion: 2025-11-01
First posted: 2021-09-27
Last updated: 2025-08-11

Locations

4 sites across 1 country: United Kingdom

Source: ClinicalTrials.gov record NCT05057013. Inclusion in this directory is not an endorsement.