Trial Title:
ARX788 for Treating Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer
NCT ID:
NCT06224673
Condition:
HER2 Low Breast Carcinoma
Triple Negative Breast Cancer
Hormone-receptor-positive Breast Cancer
Hormone Receptor Positive Breast Carcinoma
Conditions: Official terms:
Carcinoma
Breast Neoplasms
Triple Negative Breast Neoplasms
Immunoconjugates
Conditions: Keywords:
Antibody-drug Conjugate
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ARX788
Description:
Given IV
Arm group label:
Cohort 1: HR+/HER2-low
Arm group label:
Cohort 2: TNBC
Other name:
Anvatabart Opadotin
Other name:
Antibody-drug Conjugate ARX788
Other name:
Anti-Her2 Mab PAF- MMAF Toxin Oxime Conjugate ARX-788
Intervention type:
Procedure
Intervention name:
Computed Tomography (CT)
Description:
Undergo CT or Positron Emission Tomography(PET)/CT
Arm group label:
Cohort 1: HR+/HER2-low
Arm group label:
Cohort 2: TNBC
Other name:
CT Scan
Other name:
PET/CT
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Cohort 1: HR+/HER2-low
Arm group label:
Cohort 2: TNBC
Other name:
Specimen Collection
Other name:
Biological Sample Collection
Summary:
This phase II trial tests how well ARX788 works in treating patients diagnosed with
HER2-low, locally advanced unresectable or metastatic breast cancer. ARX788 is an
antibody-drug conjugate (ADC) that is given by infusion (diluted and injected slowly into
veins). Antibodies are proteins which are naturally produced by the body's immune system
to help fight infections. ARX788 consists of antibodies that have been attached to a
toxin that has the potential to kill cancer cells. ARX788 sticks to a protein called
human epidermal growth factor receptor (HER2), which is found on some breast cancer
cells. Giving ARX788 may be safe and effective in treating patients with HER2-low locally
advanced unresectable metastatic breast cancer.
Detailed description:
PRIMARY OBJECTIVES:
I. To evaluate the objective response rate (ORR) of participants with HER2-low locally
advanced unresectable/metastatic breast cancer on ARX788 monotherapy.
SECONDARY OBJECTIVES:
I. To evaluate the efficacy of ARX788 monotherapy in participants with HER2-low locally
advanced unresectable / metastatic breast cancer as measured by duration of response
(DOR), best overall response (BOR), disease control rate (DCR), progression-free survival
(PFS), and overall survival (OS).
II. To evaluate the safety of ARX788 monotherapy in participants with HER2-low locally
advanced unresectable / metastatic breast cancer (MBC).
OUTLINE:
EXPLORATORY OBJECTIVES:
I. Biomarker analyses to evaluate association of efficacy measures with potential
biomarkers (e.g., via assessment of circulating tumor deoxyribonucleic acid (ctDNA),
single cell ribonucleic acid [RNA] sequencing, etc.).
II. Patient-reported outcomes (PROs) of patients on ARX788 monotherapy. III. To determine
the feasibility, tolerability, and efficacy of eye toxicity prevention strategy.
OUTLINE:
Participants receive ARX788 intravenously (IV) over 90 minutes on day 1 of each cycle.
Cycles repeat every 21 days in the absence of disease progression or unacceptable
toxicity. Participants also undergo computed tomography (CT), positron emission
tomography (PET)/CT, and collection of blood samples throughout the study.
After completion of study treatment, participants are followed up at 30 days and then
every 3 months for 1 year.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Male or female participants age 18 years or greater with ability to provide written
informed consent for the study.
- Eastern Cooperative Oncology Group (ECOG) score of 0-2.
- Estimated life expectancy of at least at 6 months per investigator assessment.
- Ability to understand and the willingness to sign a written informed consent
document.
- Pathologically documented HER2-low locally advanced unresectable or metastatic
breast cancer. NOTE: human epidermal growth factor receptor 2 (HER2) low status
determined by HER2 immunohistochemistry (IHC) 1+ or 2+ and no evidence of HER2 gene
amplification by in situ hybridization (ISH)/fluorescence in situ hybridization
(FISH), which can be documented from any tumor sample during the patient's cancer
treatment history (early or metastatic disease).
- Cohort 1: Participants with hormone receptor positive (HR+)/HER2-low locally
advanced unresectable or metastatic breast cancer. Hormone receptor positive
status defined as estrogen receptor >= 10% and/or progesterone receptor ≥ 10%
and HER2 low.
- Cohort 2: Participants with triple negative breast cancer (TNBC), HER2-low
locally advanced unresectable or metastatic breast cancer. Considered TNBC if
estrogen receptor (ER) and progesterone receptor (PR) < 10% and HER2 low.
- Presence of at least one measurable lesion per Response Evaluation Criteria in Solid
Tumors (RECIST) version (v) 1.1. NOTE: Participant's with at least one measurable
lytic bone lesion are eligible.
- Availability of tumor block or formalin-fixed paraffin-embedded (FFPE) tissue as 10
precut unstained slides will be collected for the HER2 status evaluation and
biomarker analysis based on the most recent tumor tissue sample. NOTE: New
pretreatment biopsy tissue is preferred as HER2 status may change, but a fresh
biopsy is not required. The study team and investigator will make every attempt to
get archival tissue. Participants who do not have archival or new tumor tissue
available may be eligible after discussion with the study principal investigator
(PI).
- Participants with stable and treated brain metastases are eligible if the
participants meet the following criteria:
- Must be at least one week out from stereotactic radiosurgery and four weeks out
from whole brain radiation therapy without new or progressive neurologic
symptoms.
- Must be stable on an equivalent prednisone dose of 10mg or less daily.
- Participants must have received at least one prior line of chemotherapy or ADC
therapy for locally advanced unresectable or metastatic disease. NOTE: Prior
checkpoint inhibitor therapy is allowed.
- Hemoglobin ≥ 8 g/dL
- Absolute neutrophil count ≥ 1.0 x 10^9/L
- Platelets ≥ 100,000 x 10^9/L
- Total bilirubin ≤ 1.5 x institutional upper limit of normal, unless elevated due to
Gilbert's syndrome and direct bilirubin is within normal limits
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) <
3 x institutional upper limit of normal. In participants with liver metastases, <= 5
x institutional upper limit of normal is allowed.
- Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) < 3 x
institutional upper limit of normal. In participants with liver metastases, <=5 x
institutional upper limit of normal is allowed.
- Creatinine ≤ 1.5 x within institutional upper limit of normal OR creatinine
clearance glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m, calculated using the
Cockcroft-Gault equation
- Adequate cardiac function as assessed by left ventricular ejection fraction ≥ 50% or
institutional lower limit of normal.
- Human immunodeficiency virus (HIV)-infected individuals on effective antiretroviral
therapy with undetectable viral load within 6 months are eligible for this trial.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy.
- Individuals with a history of hepatitis C virus (HCV) infection must have been
treated without detectable HCV RNA.
- Participants must have recovered from all acute toxicities from prior therapies to ≤
grade 1 or baseline (except for alopecia and neuropathy) per the National Cancer
Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.
- Male or female participants of reproductive/childbearing potential must agree to use
a highly effective form of contraception or total sexual abstinence during and after
completion of the study for at least 8 months after the last dose of study drug.
Male participants must not freeze or donate sperm starting at screening and
throughout the study period, and at least 8 months after the final study drug
administration. Female participants must not donate, or retrieve for their own use,
ova from the time of screening and throughout the study treatment period, and for at
least 8 months after the final study drug administration.
Exclusion Criteria:
- Has a prior history of treatment with ARX-788 or auristatin analogues.
- Has a history of allergic reaction to any component of ARX788.
- Has exposure to any other investigational or commercial anti-cancer agents or
therapies administered with the intention to treat malignancy within 14 days before
the first dose of study treatment. NOTE: Anti-hormonal therapy may be administered
up to 7 days prior to the first dose of study treatment.
- Received localized palliative radiotherapy less than 7 days prior to the first dose
of ARX788 or has current radiotherapy-induced toxicity of grade 2 or greater
(excluding rash) based on NCI-CTCAE v 5.0.
- Prior or current history of interstitial lung disease (ILD), pneumonitis, or other
clinically significant lung disease with the exception of disease that is directly
attributable to the presence of lung metastases from their underlying cancer.
- Participants with significant treatment-related lung injury, defined as any of the
following:
- Any prior history of drug-induced immune-mediated pneumonitis.
- Prior history of radiation therapy to the chest of > 18 gray (Gy) with residual
sequelae considered clinically significant by investigator assessment.
- Radiographic evidence of radiation fibrosis involving > 15% of the lung
parenchyma associated with clinical symptoms.
- Has a history of keratitis, keratopathy, and/or active eye disease (excluding
glaucoma).
- Has a diagnosis of leptomeningeal carcinomatosis. NOTE: Stable brain metastases are
allowed.
- Has an active systemic or psychiatric illness that would impact the patient's
ability to receive study therapy.
- Has an uncontrollable intercurrent illness, infection (including participants with
active, symptomatic Coronavirus disease of 2019 (COVID-19) infections), or other
conditions that could limit study compliance or interfere with study assessments.
- Has a history of an additional malignancy that is progressing or has required active
treatment within the past 3 years. NOTE: Participants with basal cell carcinoma of
the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding
carcinoma in situ of the bladder, and thyroid cancer not requiring cytotoxic agents
that have undergone potentially curative therapy are not excluded.
- Participants who are pregnant or breastfeeding.
- Has an active, uncontrolled hepatitis B, hepatitis C, and/or human immunodeficiency
virus (HIV) infection. Participants with adequately controlled hepatitis B,
hepatitis C, and/or HIV are allowed. NOTE: HIV and hepatitis B and C testing are not
required for screening. Testing will only be done if clinically indicated.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California, San Francisco
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Contact:
Last name:
Amy Langdon
Phone:
415-353-7288
Email:
amy.deluca@ucsf.edu
Contact backup:
Phone:
877-827-3222
Email:
cancertrials@ucsf.edu
Investigator:
Last name:
Laura Huppert, MD
Email:
Principal Investigator
Start date:
October 15, 2024
Completion date:
February 29, 2028
Lead sponsor:
Agency:
Laura Huppert, MD, BA
Agency class:
Other
Collaborator:
Agency:
Ambrx, Inc.
Agency class:
Industry
Source:
University of California, San Francisco
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06224673
