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HER2 Low Breast CarcinomaPhase 2NCT06224673

ARX788 for Treating Patients With HER2-low Locally Advanced Unresectable or Metastatic Breast Cancer

A Phase 2 study testing ARX788, Computed Tomography (CT) and Biospecimen Collection in people with HER2 Low Breast Carcinoma and Triple Negative Breast Cancer, run by Laura Huppert, MD, BA at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ARX788, Computed Tomography (CT) and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
5 Jun 2026to 30 Nov 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • 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 and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or total sexual abstinence during and upon completion of the study; and for at least 3 months after the last dose of study drug for women of childbearing potential (WOCBP) and at least 5 months after the last dose of study drug for men whose partners are WOCBP.
  • Male subjects must agree to not freeze or donate sperm starting at Screening and throughout the study period, and at least 5 months after the final study drug administration.
  • Female subjects must agree to not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 3 months after the final study drug administration.

Who cannot join

  • 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:
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  • 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.
  • 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, carcinoma in situ (excluding carcinoma in situ of the bladder or high-grade cervical dysplasia in the last three years), and thyroid cancer not requiring cytotoxic agents that have undergone potentially curative therapy are not excluded.
  • Pregnancy 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Amy Langdon contact

(415) 353-7288

amy.deluca@ucsf.edu

United States1 site, 1 recruiting

  • University of California, San Francisco

    San Francisco, California, 94143

    Amy Langdon, (415) 353-7288, amy.deluca@ucsf.edu

    877-827-3222, cancertrials@ucsf.edu

    Recruiting

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the objective response rate (ORR) of participants with HER2-low locally advanced unresectable/metastatic breast cancer on ARX788 monotherapy.

SECONDARY OBJECTIVES:

  1. To evaluate the efficacy of ARX788 monotherapy in participants with HER2-low locally advanced unresectable or metastatic breast cancer (MBC) 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 or MBC.

III. To evaluate the safety, tolerability, adherence, and feasibility of the eye toxicity prevention regimen in the ocular toxicity prevention sub study.

IV. To evaluate the efficacy of the eye toxicity prevention regimen in the ocular toxicity prevention sub study.

EXPLORATORY OBJECTIVES:

  1. 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 pharmacokinetics (PK) of ARX788 in tears.

OUTLINE:

Participants are assigned to cohorts based on breast cancer subtype and 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. The first 5 participants successfully enrolled will receive topical amiloride 0.1% to evaluate early safety, tolerability, adherence, and feasibility data. Participants may continue study treatment until progressive disease, intolerable side effects, discontinuation due to Investigator's clinical judgment, discontinuation due to patient's choice, or the Sponsor-investigator's decision to stop the study. After completion of study treatment, participants are followed up at 30 days and then every 12 weeks for 1 year.

Being tested
ARX788, Computed Tomography (CT), Biospecimen Collection, Amiloride
Keywords
Antibody-drug Conjugate
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ARX788Drug

    Also called Anvatabart Opadotin, Antibody-drug Conjugate ARX788, Anti-Her2 Mab PAF- MMAF Toxin Oxime Conjugate ARX-788, Anti-Her2 ADC

    Given IV

  • Computed Tomography (CT)Procedure or surgery

    Also called CT Scan, PET/CT

    Undergo CT or Positron Emission Tomography(PET)/CT

  • Biospecimen CollectionProcedure or surgery

    Also called Specimen Collection, Biological Sample Collection

    Undergo collection of blood samples

  • AmilorideDrug

    Also called Amiloride Topical Eye Drops

    Ophthalmologic drops given topically to participants for an eye toxicity substudy

Study groups in NCT06224673
Study groupRoleWhat they receive
Cohort 1: HR+/HER2-lowExperimentalParticipants 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.
Receives: Drug: ARX788; Procedure: Computed Tomography (CT); Procedure: Biospecimen Collection
Cohort 2: HR-/HER2-lowExperimentalParticipants 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.
Receives: Drug: ARX788; Procedure: Computed Tomography (CT); Procedure: Biospecimen Collection
Ocular Toxicity Prevention Sub-studyExperimentalThe 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.
Receives: Drug: ARX788; Procedure: Computed Tomography (CT); Procedure: Biospecimen Collection; Drug: Amiloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 1 year

Secondary outcomes (9)

  1. Duration of response (DOR)

    Duration of response (DOR) is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first, will be computed for participants with a BOR of CR or PR. Medians and corresponding two-sided 95% confidence intervals will be reported.

    Measured: Up to 1 year

  2. Overall Best Response (BOR)

    Best overall response (BOR) is defined as the best response recorded from the start of the treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: Up to 1 year

  3. Disease Control Rate (DCR)

    The Disease control rate (DCR) is defined as the sum of PR, CR and stable disease (SD) divided by the number of response evaluable participants All-Subjects-as-Treated(AsaT).

    Measured: Up to 1 year

  4. Median Progression Free Survival (PFS)

    Progression-free survival (PFS) is defined as the time between date of first dose of study therapy and date of progression or death, whichever occurs first, will be computed for response evaluable participants (AsaT). Medians and corresponding two-sided 95% confidence intervals will be reported.

    Measured: Up to 2 years

  5. Median Overall Survival (OS)

    Overall survival (OS) is defined as the amount of time that elapses between the initiation of therapy (Cycle 1, Day 1 (C1D1) and the time of death from any cause. Medians and corresponding two-sided 95% confidence intervals will be reported.

    Measured: Up to 2 years

  6. Proportion of participants with treatment-emergent adverse events (AEs)

    Adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

    Measured: Up to 1 year

  7. Percentage of participants adhering to the eye drop

    Tolerability and adherence to eye toxicity prevention regimen will be reported as the percentage of participants who adhered to the regimen during the course of the study.

    Measured: Up to 1 year

  8. Mean score on an eye pain scale

    After each drop, participants will assess the amount of pain on a scale from 1 (lowest amount) to 10 (greatest amount). The mean and standard deviation of the pain scores by cohort will be reported

    Measured: Up to 1 year

  9. Proportion of participants reporting ocular adverse events

    The proportion of participants with a recorded grade >=2 ocular AEs based on visual acuity, eye symptoms, cornea evaluation and intraocular pressure (mmHg) readings will be reported.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2024
  2. Study start5 Jun 2026
  3. Primary completion30 Nov 2029 (estimated)
  4. Study completion30 Nov 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06224673
Sponsor's protocol ID
237527
Other IDs
NCI-2024-00073
Status last verified
Jun 2026
First submitted
16 Jan 2024
Last updated
11 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ARX788, Computed Tomography (CT) and Biospecimen Collection in people with HER2 Low Breast Carcinoma and Triple Negative Breast Cancer, run by Laura Huppert, MD, BA at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Amy Langdon ((415) 353-7288, amy.deluca@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06224673.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.

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