Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers

Sponsor

Hummingbird Bioscience (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05910827

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

Enrollment

Location

Arms

33.1

Anticipated Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 1b multi-center, open-label study of HMBD-001 in combination with docetaxel with or without cetuximab in participants with locally advanced or metastatic squamous Non-Small Cell Lung Cancers

Condition or Disease	Intervention/Treatment	Phase
Advanced or Metastatic Squamous Non-Small Cell Lung Cancer	Drug: HMBD-001 Drug: Docetaxel Drug: Cetuximab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

62 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b Study to Evaluate HMBD-001 in Combination With Docetaxel With or Without Cetuximab in Participants With Advanced Squamous Non-small Cell Lung Cancers

Anticipated Study Start Date :

Jun 30, 2023

Anticipated Primary Completion Date :

Apr 1, 2026

Anticipated Study Completion Date :

Apr 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A All participants receive HMBD-001 with docetaxel	Drug: HMBD-001 HMBD-001 is a humanized Immunoglobulin G1 (IgG1) anti-Human Epidermal Growth Factor Receptor 3(HER3) monoclonal antibody (mAb). It is administered intravenously (IV) weekly Drug: Docetaxel Docetaxel 75 mg/m^2 IV once every 3 weeks
Experimental: Arm B All participants receive HMBD-001 with docetaxel plus cetuximab	Drug: HMBD-001 HMBD-001 is a humanized Immunoglobulin G1 (IgG1) anti-Human Epidermal Growth Factor Receptor 3(HER3) monoclonal antibody (mAb). It is administered intravenously (IV) weekly Drug: Docetaxel Docetaxel 75 mg/m^2 IV once every 3 weeks Drug: Cetuximab Cetuximab 400 mg/m^2 IV loading dose, followed by 250 mg/m^2 weekly

Arm

Intervention/Treatment

Experimental: Arm A

All participants receive HMBD-001 with docetaxel

Drug: HMBD-001

HMBD-001 is a humanized Immunoglobulin G1 (IgG1) anti-Human Epidermal Growth Factor Receptor 3(HER3) monoclonal antibody (mAb). It is administered intravenously (IV) weekly

Drug: Docetaxel

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

Experimental: Arm B

All participants receive HMBD-001 with docetaxel plus cetuximab

Drug: HMBD-001

HMBD-001 is a humanized Immunoglobulin G1 (IgG1) anti-Human Epidermal Growth Factor Receptor 3(HER3) monoclonal antibody (mAb). It is administered intravenously (IV) weekly

Drug: Docetaxel

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

Drug: Cetuximab

Cetuximab 400 mg/m^2 IV loading dose, followed by 250 mg/m^2 weekly

Outcome Measures

Primary Outcome Measures

Incidence and Nature of Adverse Events (AEs) [From the time the Informed Consent Form (ICF) is signed until 30 days after last dose of study treatment]
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered to be related to the study treatment
Number of participants with dose-limiting toxicities (DLTs) [During the first three weeks of study treatment]
DLTs will be assessed during the safety run-in phase and are defined as toxicities that meet pre-defined severity criteria and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle (3 weeks) of treatment
Objective Response Rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 [Up to 24 months]
The ORR is defined as the proportion of subjects with confirmed Complete Response (CR) or confirmed Partial Response (PR), based on RECIST Version 1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Locally advanced or metastatic squamous non-small cell lung cancer for which all available standard of care treatment options have been exhausted or refused and for which at least one lesion is measurable
Tumor has known wild type status for selected genes
Have an estimated life expectancy of at least 3 months
Participants must be willing to provide a fresh tumor biopsy sample
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, docetaxel, cetuximab or any other agent that targets Epidermal Growth Factor Receptor (EGFR) or HER3, including pan-HER inhibitors
Receipt of prior targeted therapy, including but not limited to those targeting EGFR activating mutations, ALK fusions, ROS rearrangements, RET fusions or mutations, BRAF V600E mutation, MET exon 14 skipping mutation, and/or KRAS G12C mutation
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
Treatment with strong inhibitors or inducers of CYP3A4