A Phase Ib/II Study of an Anti-HER3 Antibody, HMBD-001, With Cetuximab +/- Docetaxel in Advanced Squamous Cell Cancers

Official title

A Phase Ib/II Study to Evaluate HMBD-001 in Combination With Cetuximab, With or Without Docetaxel in Participants With Advanced Squamous Cell Carcinomas

Overview

This is a Phase Ib/II multi-center, open-label study of HMBD-001 in combination with cetuximab with or without docetaxel in participants with advanced Squamous Cell Cancers

Interventions

• 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 or 60 mg/m IV once every 3 weeks
• Drug Cetuximab
  Cetuximab 250 mg/m\^2 weekly, with or without 400 mg/m\^2 IV loading dose at C1D1

Primary outcome measures

• Incidence and Nature of Adverse Events (AEs) [Time frame: 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) - applicable to part A [Time frame: From date of enrollment (first dosing) until the end of Cycle 1 (each cycle is 21 days)]
• Six months progression-free survival (PFS) - applicable to part B [Time frame: From date of enrollment (first dosing) until disease progression or death, assessed up to 6 months]

Secondary outcome measures (3)

• Objective Response Rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 [Time frame: From date of enrollment (first dosing) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months]
• HMBD-001 serum concentration-time profile and derived PK parameters [Time frame: From date of enrollment (first dosing) until date of end of treatment from any cause, including multiple treatment cycles (each cycle is 21 days), assessed up to 48 months]
• HMBD-001 Immunogenicity Profile [Time frame: From date of enrollment (first dosing) until date of end of treatment from any cause, including multiple treatment cycles (each cycle is 21 days), assessed up to 48 months]

Eligibility criteria

Inclusion criteria

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

• Males and females aged over 18 years (or having reached the age of majority according to local laws if the age of majority is \> 18 years of age)
• Eastern Cooperative Oncology Group (ECOG) status of 0 to 1
• Arm B only: 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
• Arm C only: Advanced or metastatic sqNSCLC, HNSCC, ESCC, CSCC, cervical SCC, NPC and other SCCs with at least one prior line of systemic therapy,
• 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. Prior treatment with docetaxel is allowed for Arm C

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 8 centers

• GenesisCare North Shore — Sydney
• Westmead Hospital — Westmead
• ICON Cancer Centre South Brisbane — Brisbane
• Greenslopes Private Hospital — Greenslopes
• Southern Oncology Clinical Research Unit — Adelaide
• Peninsula & South Eastern Haematology and Oncology Group — Frankston
• Cabrini Health — Malvern
• Linear Clinical Research — Perth

South Korea · 5 centers

• Chungbuk National University Hospital — Cheongju-si
• CHA Bundang Medical Center, CHA University — Seongnam-si
• Korea University Anam Hospital — Seoul
• Severance Hospital — Seoul
• The Catholic University of Korea St. Vincent's Hospital — Suwon

Taiwan · 4 centers

• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City
• National Cheng Kung University Hospital — Tainan
• Taipei Medical University - Shuang Ho Hospital — Taipei
• Taipei Veterans General Hospital — Taipei

Singapore · 2 centers

• National Cancer Centre Singapore — Singapore
• Tan Tock Seng Hospital — Singapore

Moldova · 1 center

• The Institute of Oncology, ARENSIA Exploratory Medicine Phase I Unit — Chisinau

Identifiers

NCT: NCT05910827 · HMBD-001-103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗