Clinical trial NCT05919537: Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation
Official title: A Phase 1b Study to Evaluate HMBD-001 With or Without Chemotherapy in Participants With Advanced Solid Tumors Harboring NRG1 Gene Fusions or Selected HER3 Mutations
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Pancreatic Cancer
Locally Advanced Solid Tumor
Metastatic Solid Tumor
Keywords: HMBD-001
NRG1 fusion
NRG1
Neuregulin 1
ErbB3
HER3
Lead sponsor: Hummingbird Bioscience
Sponsor class: INDUSTRY
First posted: 2023-06-26
Enrollment: 68
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 with or without chemotherapy in participants with advanced solid tumors harboring NRG1 gene fusions or selected HER3 mutations.


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

Primary outcomes:
measure: Incidence and Nature of Adverse Events (AEs)
timeFrame: From the time the ICF is signed until 30 days after last dose of study treatment
measure: Arm A and B only: Incidence and nature of dose-limiting toxicities (DLTs) during the first cycle of treatment
timeFrame: Arm A: During the first four weeks of study treatment Arm B: During the first three weeks of study treatment
measure: Objective Response Rate (ORR) by RECIST V1.1
timeFrame: Up to 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: GenesisCare North Shore
state: New South Wales
city: Brisbane
country: Australia
facility: ICON Cancer Centre South Brisbane
state: Queensland
city: Adelaide
country: Australia
facility: Southern Oncology Clinical Research Unit
state: South Australia
city: Malvern
country: Australia
facility: Cabrini Health
state: Victoria
city: Perth
country: Australia
facility: Linear Clinical Research
state: Western Australia
Study officials:
References: