Overview
This clinical trial is evaluating a drug called HMBD-001 (an anti-HER3 monoclonal antibody) in patients with advanced HER3 positive solid tumours. The main aims are to find out the maximum dose of HMBD-001 that can be given safely to patients alone and in combination with other anti-cancer agents, more about the potential side effects of HMBD-001 and how these can be treated and what happens to HMBD-001 inside the body and how it affects cancer cells.
Description
HMBD-001 is a type of drug called a monoclonal antibody, which works by targeting a protein called HER3, that is found in high numbers in some types of cancers including those which contain NRG1 gene fusions. 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 which has two parts:
Part A is a 'dose escalation' phase where small groups of patients will receive increasing doses of HMBD-001 to find the safest dose which best targets cancer cells.
- In Arm 1, patients will receive HMBD-001 on its own (as a single agent).
- In Arm 2, patients will receive HMBD-001 given with other anti-cancer drugs (in combination).
Part B is a 'dose expansion' phase where larger groups of patients with specific cancer types, known to have high levels of the protein HER3 or a confirmed NRG1 gene fusion will receive the highest doses of HMBD-001 considered to be safe in Part A either alone as single agent or in combination with other anti-cancer drugs.
The main aims of the clinical trial are to find out:
- The highest dose of HMBD-001 alone and in combination with other anti-cancer drugs that can be given safely to patients.
- 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 various combination regimens in specific tumour types of HER3 expressing tumours or tumours with NRG1 gene fusions.
Eligibility
Inclusion Criteria:
- Written (signed and dated) informed consent and be capable of co-operating with HMBD-001 administration and follow-up.
- Histologically confirmed advanced or metastatic solid tumours resistant or refractory
to conventional treatment, or for which no conventional therapy exists or is not
considered appropriate by the Investigator or is declined by the patient.
Part A Arm 1 Monotherapy Dose Escalation:
Patients with tumour types known to overexpress HER3 including:
- Bladder cancer
- Triple negative breast cancer
- Castration resistant prostate cancer
- Cervical cancer
- RAS wild type colorectal cancer
- Endometrial cancer
- Gastric cancer
- Hepatocellular carcinoma (HCC)
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Oesophageal cancer
- Ovarian Cancer
- Pancreatic cancer
- Squamous cell cancers of the head and neck
Part B Arm 1 Monotherapy Dose Expansion:
Patients with castration resistant prostate cancer, RAS wild type colorectal cancer,
triple negative breast cancer or squamous cell cancers of the head and neck with
confirmed high HER3 expression by Immunohistochemistry (IHC) on pre screening biopsy
prior to study enrolment or confirmed existing NRG1 gene fusion.
3. Life expectancy of at least 12 weeks.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Haematological and biochemical indices within the protocol specified ranges.
6. Patients with advanced prostate cancer must have castrate levels of testosterone and
have received a next generation hormonal agent (at least one of abiraterone,
enzalutamide, apalutamide or darolutamide).
7. Aged 16 years or over at the time consent is given.
Exclusion Criteria:
1. Radiotherapy (except for palliative reasons), chemotherapy, endocrine therapy (with
the exception of life-long hormone suppression such as luteinising hormone-releasing
hormone (LHRH) agents in prostate cancer), immunotherapy or investigational medicinal
products during the previous 4 weeks before trial Cycle 1 Day 1.
2. Patients with ongoing toxic manifestations of previous treatments greater than NCI
CTCAE Grade 1. Exceptions apply.
3. Patients with symptomatic brain or leptomeningeal metastases should be excluded.
Exceptions apply.
4. Women of child-bearing potential (or are already pregnant or lactating). Exceptions
apply.
5. Male patients with partners of child-bearing potential. Exceptions apply.
6. Major surgery from which the patient has not yet recovered.
7. At high medical risk because of non-malignant systemic disease including active
uncontrolled infection.
8. Known to be serologically positive for hepatitis B, hepatitis C or human
immunodeficiency virus (HIV) infection.
9. Known or suspected hypersensitivity reaction to previous biological therapy that in
the opinion of the Investigator is a contraindication for their participation in this
study.
10. Concurrent congestive heart failure, prior history of > class II cardiac disease (New
York Heart Association [NYHA]), history of clinically significant cardiac ischaemia or
prior history of clinically significant cardiac arrhythmia. Patients with significant
cardiovascular disease as defined in the protocol are excluded.
11. Patients with an active autoimmune disease including but not limited to myasthenia
gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid
arthritis, inflammatory bowel disease, vascular thrombosis associated with
antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome,
Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis.
Exceptions apply.
12. Patients receiving doses of prednisolone >10mg daily (or equipotent doses of other
corticosteroids) within 7 days prior to the first dose of study drug are not eligible
unless administered as pre-medication.
13. Patients having received a live vaccination within 4 weeks prior to first dose of HMBD
001.
14. Is a participant or plans to participate in another interventional clinical trial,
whilst taking part in this Phase I/IIa trial of HMBD-001. Participation in an
observational trial or interventional clinical trial which does not involve
administration of an IMP and which would not place an unacceptable burden on the
patient in the opinion of the Investigator and Medical Advisor would be acceptable.
15. Any other condition which in the Investigator's opinion would not make the patient a
good candidate for the clinical trial.
16. Current or prior malignancy which could affect safety or efficacy assessment of the
IMP or compliance with the protocol or interpretation of results. Patients with
curatively-treated non-melanoma skin cancer, non-muscle-invasive bladder cancer, or
carcinomas-in-situ are generally eligible.