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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Advanced or Metastatic Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: HMBD-001
* Drug: Docetaxel
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>All participants receive HMBD-001 with docetaxel | Drug: HMBD-001<br>* 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<br>Drug: Docetaxel<br>* Docetaxel 75 mg/m^2 IV once every 3 weeks<br>|
| Experimental: Arm B<br>All participants receive HMBD-001 with docetaxel plus cetuximab | Drug: HMBD-001<br>* 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<br>Drug: Docetaxel<br>* Docetaxel 75 mg/m^2 IV once every 3 weeks<br>Drug: Cetuximab<br>* Cetuximab 400 mg/m^2 IV loading dose, followed by 250 mg/m^2 weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Nature of Adverse Events (AEs) | 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 | From the time the Informed Consent Form (ICF) is signed until 30 days after last dose of study treatment | 
| Number of participants with dose-limiting toxicities (DLTs) | 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 | During the first three weeks of study treatment | 
| Objective Response Rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 | 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 | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Non-small Cell Lung Cancer, sqNSCLC, Lung, Squamous, HER3, ErbB3, Docetaxel, Cetuximab