ARX788 for Treating Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer
Phase II Open-label Study of ARX788 (Anti-HER2 Antibody Drug Conjugate (ADC)) for Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer
2 other identifiers
interventional
36
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started May 2026
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 16, 2024
CompletedFirst Posted
Study publicly available on registry
January 25, 2024
CompletedStudy Start
First participant enrolled
May 15, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2029
Study Completion
Last participant's last visit for all outcomes
September 30, 2029
May 1, 2026
April 1, 2026
3.4 years
January 16, 2024
April 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Objective response rate (ORR)
Objective response rate (ORR) is defined as the proportion of participants who experience complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The ORR and corresponding two-sided exact 90% confidence intervals will be reported.
Up to 1 year
Secondary Outcomes (9)
Duration of response (DOR)
Up to 1 year
Overall Best Response (BOR)
Up to 1 year
Disease Control Rate (DCR)
Up to 1 year
Median Progression Free Survival (PFS)
Up to 2 years
Median Overall Survival (OS)
Up to 2 years
- +4 more secondary outcomes
Study Arms (3)
Cohort 1: HR+/HER2-low
EXPERIMENTALParticipants with locally advanced, unresectable MBC that is hormone receptor (HR) positive (HR+) /human epidermal growth factor receptor 2 (HER2)-low will receive ARX788 intravenously 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 CT, PET/CT, and collection of blood samples throughout the study.
Cohort 2: HR-/HER2-low
EXPERIMENTALParticipants with confirmed HR negative (HR-)/human epidermal growth factor receptor 2 (HER2)-low will receive ARX788 intravenously 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 CT, PET/CT, and collection of blood samples throughout the study.
Ocular Toxicity Prevention Sub-study
EXPERIMENTALThe first 5 participants from Cohorts 1 and 2 will be given outpatient eye drops to use from home in conjunction with ARX788. Participants will be drop applied to each eye 4 times a day starting on the day of first infusion and continuing daily throughout treatment and for 30 days after the last infusion.
Interventions
Given IV
Undergo CT or Positron Emission Tomography(PET)/CT
Undergo collection of blood samples
Ophthalmologic drops given topically to participants for an eye toxicity substudy
Eligibility Criteria
You may qualify if:
- 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 (MBC). 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-stage or metastatic).
- Cohort 1: Participants with hormone receptor positive (HR+)/HER2-low locally advanced unresectable or MBC. HR+ status defined as estrogen receptor \>= 10% and/or progesterone receptor ≥ 10% and HER2 low.
- Cohort 2: Participants with hormone receptor negative (HR-)/HER2-low locally advanced unresectable or MBC. Considered HR- 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:
- Prior stereotactic radiosurgery (SRS) should be completed \>=7 days before study treatment initiation.
- Prior whole-brain radiation therapy should be completed \>=14 days before study treatment initiation.
- Any ongoing use of systemic corticosteroids does not exceed 2 mg of dexamethasone (or equivalent) daily.
- Participants must have received at least one prior line of chemotherapy or ADC therapy for locally advanced unresectable or metastatic disease. Prior checkpoint inhibitor therapy is allowed.
- Hemoglobin ≥ 8.0 g/dL
- +14 more criteria
You may not qualify if:
- 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.
- Radiotherapy outside of the brain administered \<7 days prior to first dose of ARX788
- 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 pulmonary conditions, 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.
- Any requirement for supplemental oxygen.
- Clinically-significant ocular findings including history of keratitis, keratopathy, and/or active eye disease (excluding glaucoma).
- History of congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or myocardial infarction within 6 months prior to enrollment. QTcF prolongation of \>470 msec (females) or \>450 msec (males) based screening ECG.
- 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.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Laura Huppert, MD, BAlead
- Ambrx, Inc.collaborator
Study Sites (1)
University of California, San Francisco
San Francisco, California, 94143, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Laura Huppert, MD
University of California, San Francisco
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
January 16, 2024
First Posted
January 25, 2024
Study Start (Estimated)
May 15, 2026
Primary Completion (Estimated)
September 30, 2029
Study Completion (Estimated)
September 30, 2029
Last Updated
May 1, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share