Trial Title:
A Phase I/IIa Trial of HMBD-001 in Advanced HER3 Positive Solid Tumours
NCT ID:
NCT05057013
Condition:
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 Cancer of the Head and Neck
Conditions: Official terms:
Endometrial Neoplasms
Triple Negative Breast Neoplasms
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Conditions: Keywords:
Antibodies, monoclonal
HER3
Receptor, ErbB-3
NRG1
NRG1 gene fusion
Neuregulin 1
Androgen receptor antagonists
Prostatic neoplasms, castration-resistant
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
HMBD-001
Description:
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.
Arm group label:
HMBD-001 (Part A)
Intervention type:
Drug
Intervention name:
HMBD-001 and enzalutamide
Description:
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.
Arm group label:
HMBD-001 and enzalutamide (Part B Arm 1)
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.
Criteria for eligibility:
Criteria:
Inclusion criteria:
1. Written (signed and dated) informed consent and be capable of co-operating with
HMBD-001 administration and follow-up.
2. Part A: Monotherapy Dose Escalation
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 participant.
Participants 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
Participants with confirmed existing NRG1 fusion rearrangement will also be
considered eligible.
Part B Arm 1: HMBD-001 and Enzalutamide Combination
- Histologically confirmed metastatic castration-resistant prostate
adenocarcinoma without neuroendocrine differentiation or small-cell features.
- Serum testosterone concentration ≤50 ng/dL sustained by medical or surgical
castration.
- Participants must have progressive disease prior to study enrolment.
- PSA at screening ˃1 ng/mL.
- Confirmed high HER3 expression.
- Absence of PTEN loss.
- Participants with confirmed existing NRG1 fusion rearrangement will also be
considered eligible.
3. Life expectancy of at least 12 weeks.
4. Eastern Cooperative Oncology Group performance status of 0 or 1.
5. Haematological and biochemical indices within the protocol specified ranges.
6. Participants 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. Part A: Aged 16 years or over at the time consent is given.
8. Part B Arm 1: Aged 18 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 agents in prostate cancer), immunotherapy or investigational medicinal
products during the previous 4 weeks before first dose of HMBD-001 or enzalutamide,
as applicable.
2. Participants with ongoing toxic manifestations of previous treatments greater than
NCI CTCAE Grade 1. Exceptions apply.
3. Participants 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 participants with partners of child-bearing potential. Exceptions apply.
6. Major surgery from which the participant 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 infection. Participants with previous hepatitis C exposure
but no current infection are eligible to participate.
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), clinically significant cardiac ischaemia or clinically
significant cardiac arrhythmia. Participants with significant cardiovascular disease
as defined in the protocol are excluded.
11. Active autoimmune disease. Exceptions apply.
12. Participants receiving doses of prednisolone ˃10 mg 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. Participants 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 1/2a 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
participant 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
participant 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. Participants with
curatively-treated non-melanoma skin cancer, non-muscle-invasive bladder cancer, or
carcinomas-in-situ are generally eligible.
Part B Arm 1: HMBD-001 and Enzalutamide Combination:
17. Participants receiving warfarin or coumarin-like anti-coagulants.
18. History of seizures or other risk factors for the development of seizures e.g. prior
history of stroke, brain injury, brain metastases, leptomeningeal disease.
19. Participants with hypersensitivity to enzalutamide or any of the excipients
20. Participants who have received prior enzalutamide or other next generation hormonal
agent that has been stopped due to toxicities or intolerance or required a dose
reduction during administration due to toxicity or intolerance.
Gender:
All
Minimum age:
16 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Royal Marsden NHS Foundation Trust
Address:
City:
London
Zip:
SM2 5PT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Johann de Bono, Prof
Email:
Johann.DeBono@icr.ac.uk
Facility:
Name:
The Christie Hospital
Address:
City:
Manchester
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Louise Carter, Dr
Email:
louise.carter24@nhs.net
Facility:
Name:
Freeman Hospital, Newcastle
Address:
City:
Newcastle
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Alastair Greystoke, Dr
Email:
alastair.greystoke@newcastle.ac.uk
Facility:
Name:
Churchill Hospital
Address:
City:
Oxford
Zip:
OX3 7LE
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Simon Lord, Dr
Email:
simon.lord@oncology.ox.ac.uk
Start date:
November 10, 2021
Completion date:
September 2026
Lead sponsor:
Agency:
Cancer Research UK
Agency class:
Other
Collaborator:
Agency:
Hummingbird Bioscience
Agency class:
Industry
Source:
Cancer Research UK
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05057013
