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

NCT05057013 | Active Not Recruiting Phase 1

• 2 other identifiers: CRUKD/22/0022020-005891-36
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

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

Keywords

Antibodies, monoclonal; HER3; Receptor, ErbB-3; NRG1; NRG1 gene fusion; Neuregulin 1; Androgen receptor antagonists; Prostatic neoplasms, castration-resistant

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (13)

• ORR within 6 cycles of HMBD-001 (Part A)

  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)

  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)

  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)

  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)

  Up to 31 timepoints from first dose until 28 days after the last dose of HMBD-001 (max 28 weeks per participant)

Study Arms (2)

HMBD-001 (Part A)

EXPERIMENTAL

Drug: HMBD-001

HMBD-001 and enzalutamide (Part B Arm 1)

EXPERIMENTAL

Drug: HMBD-001 and enzalutamide

Interventions

HMBD-001 DRUG

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.

HMBD-001 (Part A)

HMBD-001 and enzalutamide DRUG

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.

HMBD-001 and enzalutamide (Part B Arm 1)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• Participants with ongoing toxic manifestations of previous treatments greater than NCI CTCAE Grade 1. Exceptions apply.
• Participants with symptomatic brain or leptomeningeal metastases should be excluded. Exceptions apply.
• Women of child-bearing potential (or are already pregnant or lactating). Exceptions apply.
• Male participants with partners of child-bearing potential. Exceptions apply.
• Major surgery from which the participant has not yet recovered.
• At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
• 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.
• 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.
• 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.
• Active autoimmune disease. Exceptions apply.
• 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.
• Participants having received a live vaccination within 4 weeks prior to first dose of HMBD-001.
• 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.
• Any other condition which in the Investigator's opinion would not make the participant a good candidate for the clinical trial.

Sponsors & Collaborators

• Cancer Research UK: lead
• Hummingbird Bioscience: collaborator

Study Sites (4)

Royal Marsden NHS Foundation Trust

London, SM2 5PT, United Kingdom

Location

The Christie Hospital

Manchester, United Kingdom

Location

Freeman Hospital, Newcastle

Newcastle, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Triple Negative Breast Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms; Stomach Neoplasms; Carcinoma, Hepatocellular; Melanoma; Carcinoma, Non-Small-Cell Lung; Esophageal Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Lethal Congenital Contracture Syndrome 2; Fibromatosis, Gingival, 2; Prostatic Neoplasms, Castration-Resistant

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Genital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Head and Neck Neoplasms; Esophageal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Pancreatic Diseases; Prostatic Neoplasms; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases

Study Officials

• Johann de Bono, Prof

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2021
• First Posted: September 27, 2021
• Study Start: November 10, 2021
• Primary Completion: November 1, 2025
• Study Completion: November 1, 2025
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4)