ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03)

Key Inclusion Criteria:

• Age ≥ 18 years and older

• Life expectancy ≥ 6 months

• Unresectable or metastatic breast cancer subjects

• Presence of at least one measurable lesion per RECIST v 1.1

• Subjects must have HER2 positive breast cancer per ASCO-CAP guidelines, documentedin a CLIA lab pathology report

• Subjects must have had prior treatment with no more than 5 prior regimens ofsystemic treatment HER-2 targeting therapy or chemotherapy in the metastaticsetting. One of these prior treatments must have been treatment with T-DXd.

• Subjects with stable brain metastases

• Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolvedto Grade ≤1 as per the NCI-CTCAE v 5.0, except alopecia, vitiligo, Grade 2peripheral neuropathy, or endocrine toxicities that are stable on hormonereplacement.

• Adequate organ functions

• Willing and able to understand and sign an informed consent inform and to complywith all aspects of the protocol

Key Exclusion Criteria:

Any subject who meets any of the following criteria is excluded from the study:

• History of allergic reactions to any component of ARX788.

• Prior history of interstitial lung disease, pneumonitis, or other clinicallysignificant lung disease. Any requirement for supplemental oxygen.

• Any active ocular infections or chronic corneal disorders

• History of congestive heart failure, unstable angina pectoris, unstable atrialfibrillation, cardiac arrhythmia, or myocardial infarction within 6 months prior toenrollment

• Grade 3 to 4 peripheral neuropathy (NCI CTCAE v 5.0).

• History of unstable central nervous system (CNS) metastases

• Radiotherapy outside of the brain administered < 7 days prior to first dose ofARX788

• Current severe, uncontrolled systemic disease (eg, clinically significantcardiovascular, pulmonary, or metabolic diseases)

• Any uncontrollable intercurrent illness, infection (including subjects with active,symptomatic Covid-19 infections), or other conditions that could limit studycompliance or interfere with assessments

• Exposure to any other investigational or commercial anticancer agents or therapiesadministered with the intention to treat malignancy within 14 days before the firstdose of ARX788