ARX788 for Treating 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.

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 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: 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 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.