HMBD-001 in Advanced HER3 Positive Solid Tumours

March 20, 2023 updated by: Cancer Research UK

HMBD-001 (an Anti-HER3 Monoclonal Antibody) Given Intravenously as a Single Agent and in Combination in Patients With Advanced HER3 Positive Solid Tumours

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

135

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

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.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Written (signed and dated) informed consent and be capable of co-operating with HMBD-001 administration and follow-up.

  2. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A Arm 1 Dose Escalation (single agent)
Groups of patients will receive increasing doses of HMBD-001 as a single agent to find a safe dose that best targets cancer cells. Approximately 26 patients with tumours known to express HER3 will be entered into this arm.
Drug: HMBD-001
Intravenous infusion given over a 21 or 28 day cycle dependent on dosing frequency. Number of cycles: 6 or until disease progression or unacceptable toxicity develops.
Experimental: Part B Arm 1 Dose Expansion (single agent)
An expansion cohort of up to 25 patients with a confirmed HER3 positive or confirmed NRG1 fusion rearrangement RAS wild type colorectal cancer, castration resistant prostate cancer, triple negative breast cancer or squamous cell head and neck cancer will receive the HMBD-001 single agent RP2D as determined in Part A Arm 1.
Drug: HMBD-001
Intravenous infusion given over a 21 or 28 day cycle dependent on dosing frequency. Number of cycles: 6 or until disease progression or unacceptable toxicity develops.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recommended Phase II dose (Part A)
Time Frame: When sufficient patients have had the opportunity to complete 1 Cycle (max 28 days)
Recommended dose of HMBD-001 given a) as a single agent and b) in combination with selected anticancer agent(s) with an estimated Dose Limiting Toxicity (DLT) rate that is closest to 25% using a one-stage Bayesian Continual Reassessment Method (CRM)
When sufficient patients have had the opportunity to complete 1 Cycle (max 28 days)
Number of grade 3, 4 and 5 adverse events related to HMBD-001 (Part A & B)
Time Frame: When sufficient patients have had the opportunity to complete 1 Cycle (max 28 days)
Number of grade 3, 4 and adverse events related to HMBD-001 given a) as a single agent and b) in combination with selected anti-cancer agent(s) graded according to National Cancer Institute Common Criteria for Adverse Events (NCI CTCAE) Version 5.0
When sufficient patients have had the opportunity to complete 1 Cycle (max 28 days)
Number of patients achieving a complete response (CR) or partial response (PR) to HMBD-001 in the chosen tumour types (Part B)
Time Frame: From baseline radiological disease assessment until 28 days after last dose of HMBD-001 (max 30 weeks) per patient
Number of patients achieving a complete response (CR) or partial response (PR) to HMBD-001 based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 in the chosen tumour types
From baseline radiological disease assessment until 28 days after last dose of HMBD-001 (max 30 weeks) per patient

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum observed plasma concentration (Cmax) of HMBD-001 (Part A & B)
Time Frame: From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Maximum observed plasma concentration (Cmax) of HMBD-001
From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Area under the curve (AUC) of HMBD-001 (Part A & B)
Time Frame: From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Area under the curve (AUC) of HMBD-001
From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Terminal elimination half-life (t½) of HMBD-001 (Part A & B)
Time Frame: From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Terminal elimination half-life (t½) of HMBD-001
From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Time taken to reach maximum observed concentration (Tmax) of HMBD-001 (Part A & B)
Time Frame: From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Time taken to reach maximum observed concentration (Tmax) of HMBD-001
From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Steady state volume of distribution of HMBD-001 in plasma (Part A and B)
Time Frame: From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Volume of distribution of HMBD-001 in plasma
From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Total body clearance of HMBD-001 (Part A and B)
Time Frame: From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Total body clearance of HMBD-001
From first dose of HMBD-001 until 24 weeks after first dose of HMD-001
Number of patients achieving a complete response (CR), partial response (PR) or stable disease (SD) based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 (Part A and B)
Time Frame: From baseline radiological disease assessment until 28 days after last dose of HMBD-001 (max 30 weeks) per patient
Number of patients achieving a complete response (CR), partial response (PR) or stable disease (SD) based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
From baseline radiological disease assessment until 28 days after last dose of HMBD-001 (max 30 weeks) per patient
Number of Patients whose cancer has not progressed at 12 and 24 months (Part A & B)
Time Frame: From first dose of HMBD-001 until 24 months after first dose of HMBD-001
Number of Patients whose cancer has not progressed at 12 and 24 months
From first dose of HMBD-001 until 24 months after first dose of HMBD-001
Number of patients who are still alive at 12 and 24 months (Part A & B)
Time Frame: From first dose of HMBD-001 until 24 months after first dose of HMBD-001
Number of patients who are still alive at 12 and 24 months
From first dose of HMBD-001 until 24 months after first dose of HMBD-001

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cancer Research UK

Collaborators

Hummingbird Bioscience

Investigators

  • Study Director: Derek Paisley, Cancer Research UK
  • Principal Investigator: Johaan de Bono, Prof, Royal Marsden NHS Foundation Trust

Study record dates

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 Major Dates

Study Start (Actual)

November 10, 2021

Primary Completion (Anticipated)

September 1, 2026

Study Completion (Anticipated)

September 1, 2026

Study Registration Dates

First Submitted

September 10, 2021

First Submitted That Met QC Criteria

September 24, 2021

First Posted (Actual)

September 27, 2021

Study Record Updates

Last Update Posted (Actual)

March 21, 2023

Last Update Submitted That Met QC Criteria

March 20, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRUKD/22/002
  • 2020-005891-36 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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