Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation

NCT ID: NCT05919537

Last Updated: 2025-04-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-06
• Study Completion Date: 2031-03-01

Brief Summary

This is a phase 1b multi-center, open-label study of HMBD-001 with or without chemotherapy in participants with advanced solid tumors harboring NRG1 gene fusions or selected HER3 mutations.

Conditions

Non-Small Cell Lung Cancer; Pancreatic Cancer; Locally Advanced Solid Tumor; Metastatic Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Participants with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) harboring NRG1 gene fusions

Group Type: EXPERIMENTAL

HMBD-001

Intervention Type: DRUG

HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly

Nab-paclitaxel

Intervention Type: DRUG

Nab-paclitaxel 125 mg/m\^2 IV on days 1, 8, 15, every 4 weeks

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000 mg/m\^2 IV on days 1, 8, 15, every 4 weeks

Arm B

Participants with non-small cell lung cancer (NSCLC) harboring NRG1 gene fusions

Group Type: EXPERIMENTAL

HMBD-001

Intervention Type: DRUG

HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly

Docetaxel

Intervention Type: DRUG

Docetaxel 75 mg/m\^2 IV once every 3 weeks

Arm C

Participants with other solid tumors harboring NRG1 gene fusions

Group Type: EXPERIMENTAL

HMBD-001

Intervention Type: DRUG

HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly

Arm D

Participants with solid tumors harboring selected HER3 extracellular mutations

Group Type: EXPERIMENTAL

HMBD-001

Intervention Type: DRUG

HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly

Interventions

HMBD-001

HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly

Intervention Type: DRUG

Docetaxel

Docetaxel 75 mg/m\^2 IV once every 3 weeks

Intervention Type: DRUG

Nab-paclitaxel

Nab-paclitaxel 125 mg/m\^2 IV on days 1, 8, 15, every 4 weeks

Intervention Type: DRUG

Gemcitabine

Gemcitabine 1000 mg/m\^2 IV on days 1, 8, 15, every 4 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Ability to understand and be willing to sign an informed consent form

• Males and females aged over 18 years
• Eastern Cooperative Oncology Group (ECOG) status of 0 to 1
• Histologic or cytologic evidence of an advanced malignant solid that is resistant/refractory to standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy in the physician's judgment likely to result in clinical benefit, or the participant has demonstrated to be intolerable to such therapy, or if such therapy has been refused by the participant
• Arms A, B and C: Cancer harboring an NRG1 gene fusion with EGF-like domain; Arm A: Participants with locally advanced or metastatic pancreatic adenocarcinoma that have not received prior treatment with gemcitabine or nab-paclitaxel and /or have not received more than 2 lines of systemic therapy for advanced disease; Arm B: Participants with locally advanced or metastatic non-small cell lung cancer that have not received prior treatment with docetaxel and /or have not received more than 2 lines of systemic therapy for advanced disease; Arm C: Participants must not be eligible to participate in Arm A or B
• Arm D: Cancer harboring selected HER3 mutations limited to the extracellular domain.
• Have an estimated life expectancy of at least 3 months
• Have an archival tumour sample available or have a site of disease amenable to biopsy and be willing to undergo a biopsy prior to the receipt of the assigned study treatment
• Have adequate organ function
• Females must be non-pregnant and non-lactating, willing to use a highly effective method of contraception from screening until study completion or be either surgically sterile or post-menopausal
• Males must be surgically sterile, abstinent, or if engaged in sexual relations with a woman of child-bearing potential, the participant and his partner must be surgically sterile or using an acceptable, highly effective contraceptive method from screening until study completion

Exclusion Criteria

• Prior treatment with HMBD-001, pertuzumab, or an agent that specifically targets HER3, including pan-HER tyrosine kinase inhibitors

• Persistent clinically significant toxicities (Grade ≥2) from previous anti-cancer therapy except for Grade >2 toxicities that are considered unlikely to put the participant at an increased risk of treatment-related toxicity and/or impact the study results e.g., alopecia
• Most recent anti-cancer therapy including radiotherapy at least 4 weeks, or nitrosourea or mitomycin 3 at least 6 weeks, or 5 half-lives whichever is shorter prior to starting the assigned study treatment
• Symptomatic primary Central Nervous System (CNS) cancer or metastases unless the symptoms are stable for at least 28 days prior to the first dose of the study drug and any symptoms have returned to baseline
• Evidence of abnormal cardiac function
• History of uncontrolled allergic reactions and/or known expected hypersensitivity to the study drugs used in the treatment arm to which the participant is to be enrolled into
• Any other known active malignancy except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer
• Any uncontrolled illness or significant uncontrolled condition(s) requiring systemic treatment
• Known Human Immunodeficiency Virus (HIV) infection
• Active hepatitis B or hepatitis C infection
• Pregnant or breast feeding
• COVID 19 infection within 3 months prior to the first dose of the study drug
• COVID 19 vaccination within 14 days prior to the first dose of the study drug

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hummingbird Bioscience

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

GenesisCare North Shore

Sydney, New South Wales, Australia

ICON Cancer Centre South Brisbane

Brisbane, Queensland, Australia

Southern Oncology Clinical Research Unit

Adelaide, South Australia, Australia

Cabrini Health

Malvern, Victoria, Australia

Linear Clinical Research

Perth, Western Australia, Australia

Countries

Australia

Other Identifiers

HMBD-001-102

Identifier Type: -

Identifier Source: org_study_id