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

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 (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).
• •* 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.