Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Uterine Cervical Neoplasms

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Pancreatic Neoplasms

Melanoma

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Stomach Neoplasms

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Lung Neoplasms

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Endometrial Neoplasms

Neoplasms, Squamous Cell

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

Neoplasms by Histologic Type

Skin Diseases

Neoplasms, Glandular and Epithelial

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Uterine Neoplasms

Uterine Diseases

Breast Diseases

Esophageal Cancer

Pancreatic Cancer

Ovarian Cancer

Stomach Cancer

Ovarian Epithelial Cancer

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

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.

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.

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.

HMBD-001

Johann de Bono, Prof

Simon Lord, Dr

Derek Paisley

Johaan de Bono, Prof

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.

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.

HMBD-001 in Advanced HER3 Positive Solid Tumours

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

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)

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

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

Maximum observed plasma concentration (Cmax) of HMBD-001

Terminal elimination half-life (t½) of HMBD-001

Time taken to reach maximum observed concentration (Tmax) of HMBD-001

Volume of distribution of HMBD-001 in plasma

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

Number of Patients whose cancer has not progressed at 12 and 24 months

Number of patients who are still alive at 12 and 24 months

Spots Global Cancer Trial Database for nrg1 gene fusion