Clinical trial NCT05910827: Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers, and HMBD-001 + Cetuximab in Advanced Squamous Cell Cancers
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, and HMBD-001 in Combination With Cetuximab in Participants With Advanced Squamous Cell Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced or Metastatic Squamous Non-Small Cell Lung Cancer
Advanced Head and Neck Squamous Cell Carcinoma
Advanced Esophageal Squamous Cell Carcinoma
Cervical Squamous Cell Carcinoma
Advanced Cutaneous Squamous Cell Carcinoma
Keywords: NSCLC
Non-small Cell Lung Cancer
sqNSCLC
Lung
Squamous
HER3
ErbB3
Docetaxel
Cetuximab
cervical squamous cell carcinoma
HNSCC
CSCC
ESCC
advanced squamous cell cancer
Lead sponsor: Hummingbird Bioscience
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2023-06-20
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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, and HMBD-001 in combination with cetuximab in participants with advanced Squamous Cell Cancers


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 \&gt; 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 or cervical SCC 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 \&gt;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

Primary outcomes:
measure: Incidence and Nature of Adverse Events (AEs)
timeFrame: From the time the Informed Consent Form (ICF) is signed until 30 days after last dose of study treatment
measure: Objective Response Rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) V1.1
timeFrame: Up to 24 months
measure: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: During the first three weeks of study treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: GenesisCare North Shore
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: ICON Cancer Centre South Brisbane
state: Queensland
city: Greenslopes
country: Australia
facility: Greenslopes Private Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Southern Oncology Clinical Research Unit
state: South Australia
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Health
state: Victoria
city: Perth
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Chisinau
country: Moldova, Republic of
facility: The Institute of Oncology, ARENSIA Exploratory Medicine Phase I Unit
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
Study officials:
References: